Sample records for alcohol withdrawal severity

  1. Review of adjunctive dexmedetomidine in the management of severe acute alcohol withdrawal syndrome.

    PubMed

    Wong, Adrian; Smithburger, Pamela L; Kane-Gill, Sandra L

    2015-01-01

    The primary management of alcohol withdrawal involves the administration of a γ-aminobutyric acid agonist, such as benzodiazepines, for management of symptoms and to prevent further progression to seizure or delirium tremens. Despite escalating doses of benzodiazepines, published literature indicates that some patient's alcohol withdrawal syndrome symptoms do not respond, and that the use of adjunctive agents may be beneficial in these patients. Dexmedetomidine, an α2-agonist, serves as a potential adjunctive agent through management of associated autonomic symptoms. Understanding of recent literature evaluating its use is necessary for appropriate selection. To review available literature supporting the use of adjunctive dexmedetomidine for management of severe alcohol withdrawal syndrome. A total of 13 published articles evaluating the efficacy and safety of dexmedetomidine as an adjunctive agent for the treatment of alcohol withdrawal in adult patients were identified from a MEDLINE search using the key words alcohol withdrawal, delirium tremens and dexmedetomidine. Evaluation of the literature indicates that dexmedetomidine is associated with a decrease in short-term benzodiazepine requirements after initiation, and improvement in hemodynamic parameters in relation to the adrenergic drive present in alcohol withdrawal. The use of dexmedetomidine in the management of severe alcohol withdrawal should be considered as an adjunctive agent. Dexmedetomidine appears to be well tolerated, with an expected decrease in blood pressure and heart rate. Seizures have occurred in patients with alcohol withdrawal despite the use of dexmedetomidine, with and without benzodiazepines, due to lack of γ-aminobutyric acid agonist administration.

  2. Nicotinic Mechanisms Modulate Ethanol Withdrawal and Modify Time Course and Symptoms Severity of Simultaneous Withdrawal from Alcohol and Nicotine.

    PubMed

    Perez, Erika; Quijano-Cardé, Natalia; De Biasi, Mariella

    2015-09-01

    Alcohol and nicotine are among the top causes of preventable death in the United States. Unfortunately, people who are dependent on alcohol are more likely to smoke than individuals in the general population. Similarly, smokers are more likely to abuse alcohol. Alcohol and nicotine codependence affects health in many ways and leads to poorer treatment outcomes in subjects who want to quit. This study examined the interaction of alcohol and nicotine during withdrawal and compared abstinence symptoms during withdrawal from one of the two drugs only vs both. Our results indicate that simultaneous withdrawal from alcohol and nicotine produces physical symptoms that are more severe and last longer than those experienced during withdrawal from one of the two drugs alone. In animals experiencing withdrawal after chronic ethanol treatment, acute nicotine exposure was sufficient to prevent abstinence symptoms. Similarly, symptoms were prevented when alcohol was injected acutely in mice undergoing nicotine withdrawal. These experiments provide evidence for the involvement of the nicotinic cholinergic system in alcohol withdrawal. Furthermore, the outcomes of intracranial microinfusions of mecamylamine, a nonselective nicotinic receptor antagonist, highlight a major role for the nicotinic receptors expressed in medial habenula and interpeduncular nucleus during withdrawal. Overall, the data support the notion that modulating the nicotinic cholinergic system might help to maintain long-term abstinence from alcohol.

  3. Alcohol withdrawal

    MedlinePlus

    ... Seeing or feeling things that aren't there (hallucinations) Seizures Severe confusion ... alcohol withdrawal. You will be watched closely for hallucinations and other signs of delirium tremens. Treatment may ...

  4. Alcohol Withdrawal Syndrome: Benzodiazepines and Beyond

    PubMed Central

    Sachdeva, Ankur; Chandra, Mina

    2015-01-01

    Alcohol dependence is an increasing and pervasive problem. Alcohol withdrawal symptoms are a part of alcohol dependence syndrome and are commonly encountered in general hospital settings, in most of the departments. Alcohol withdrawal syndrome ranges from mild to severe. The severe complicated alcohol withdrawal may present with hallucinations, seizures or delirium tremens. Benzodiazepines have the largest and the best evidence base in the treatment of alcohol withdrawal, and are considered the gold standard. Others, such as anticonvulsants, barbiturates, adrenergic drugs, and GABA agonists have been tried and have evidence. Supportive care and use of vitamins is essential in the management. Symptom triggered regime is favoured over fixed tapering dose regime, although monitoring through scales is cumbersome. This article aims to review the evidence base for appropriate clinical management of the alcohol withdrawal syndrome. We searched Pubmed for articles published in English on ‘Alcohol withdrawal syndrome’ in humans during the last 10 years. A total of 1182 articles came up. Articles not relevant to clinical utility and management were excluded based on the titles and abstract available. Full text articles, meta-analyses, systematic reviews and randomized controlled trials were obtained from this list and were considered for review. PMID:26500991

  5. Anticonvulsants for alcohol withdrawal.

    PubMed

    Minozzi, Silvia; Amato, Laura; Vecchi, Simona; Davoli, Marina

    2010-03-17

    from one study, 72 participants, favour paraldehyde plus chloral hydrate versus chlordiazepoxide, for the severe-life threatening side effects, RR 0.12 (0.03 to 0.44). Results of this review do not provide sufficient evidence in favour of anticonvulsants for the treatment of AWS. There are some suggestions that carbamazepine may actually be more effective in treating some aspects of alcohol withdrawal when compared to benzodiazepines, the current first-line regimen for alcohol withdrawal syndrome. Anticonvulsants seem to have limited side effects, although adverse effects are not rigorously reported in the analysed trials.

  6. Effects of acute alcohol withdrawal on nest building in mice selectively bred for alcohol withdrawal severity

    PubMed Central

    Greenberg, Gian D.; Phillips, Tamara J.; Crabbe, John C.

    2017-01-01

    Nest building has been used to assess thermoregulatory behavior and positive motivational states in mice. There are known genetic influences on ethanol withdrawal severity as well as individual/thermoregulatory nest building. Withdrawal Seizure-Prone (WSP-1, WSP-2) and Withdrawal Seizure-Resistant (WSR-1, WSR-2) mice were selectively bred for high vs low handling-induced convulsion (HIC) severity, respectively, during withdrawal from chronic ethanol vapor inhalation. They also differ in HIC severity during withdrawal from an acute, 4 g/kg ethanol injection. In our initial study, withdrawal from an acute dose of ethanol dose-dependently impaired nest building over the initial 24 h of withdrawal in genetically segregating Withdrawal Seizure Control (WSC) mice. In two further studies, acute ethanol withdrawal suppressed nest building for up to two days in WSP-1 females. Deficits in nest building from ethanol were limited to the initial 10 h of withdrawal in WSR-1 females and to the initial 24 h of withdrawal in WSP-1 and WSR-1 males. Effects of ethanol on nest building for up to two days were found in WSP-2 and WSR-2 mice of both sexes. Nest building deficits in female mice from the first replicate could not be explained by a general decrease in locomotor behavior. These results suggest that nest building is a novel behavioral phenotype for indexing the severity of acute ethanol withdrawal, and that genes contributing to this trait differ from those affecting acute withdrawal HIC severity. PMID:27503811

  7. Increased QT interval variability index in acute alcohol withdrawal.

    PubMed

    Bär, Karl-Jürgen; Boettger, Michael Karl; Koschke, Mandy; Boettger, Silke; Grotelüschen, Marei; Voss, Andreas; Yeragani, Vikram K

    2007-07-10

    Acute alcohol withdrawal is associated with increased cardiovascular mortality, most likely due to cardiac arrhythmias. As the QT interval reflects the most critical phase for the generation of reentry and thus for arrhythmia, we examined QT variability in patients suffering from acute alcohol withdrawal. High resolution electrocardiographic recordings were performed in 18 male unmedicated patients suffering from acute alcohol withdrawal, 18 matched controls and 15 abstained alcoholics. From these, parameters of beat-to-beat heart rate and QT variability such as approximate entropy and QT variability index (QTvi) were calculated. Measures were correlated with the severity of withdrawal symptoms and with serum electrolyte concentrations. Heart rate and QTvi were significantly increased in acute alcohol withdrawal. Abstained alcoholics did not significantly differ from controls. While QTvi correlated with the severity of alcohol withdrawal symptoms, the mean QT interval duration showed an inverse relationship with serum potassium concentrations. Our data indicate increased QT variability and thus increased repolarization lability in acute alcohol withdrawal. This might add to the elevated risk for serious cardiac arrhythmias. In part, these changes might be related to increased cardiac sympathetic activity or low potassium, thus suggesting the latter as possible targets for adjuvant pharmacological therapy during withdrawal.

  8. Effects of acute alcohol withdrawal on nest building in mice selectively bred for alcohol withdrawal severity.

    PubMed

    Greenberg, Gian D; Phillips, Tamara J; Crabbe, John C

    2016-10-15

    Nest building has been used to assess thermoregulatory behavior and positive motivational states in mice. There are known genetic influences on ethanol withdrawal severity as well as individual/thermoregulatory nest building. Withdrawal Seizure-Prone (WSP-1, WSP-2) and Withdrawal Seizure-Resistant (WSR-1, WSR-2) mice were selectively bred for high vs low handling-induced convulsion (HIC) severity, respectively, during withdrawal from chronic ethanol vapor inhalation. They also differ in HIC severity during withdrawal from an acute, 4g/kg ethanol injection. In our initial study, withdrawal from an acute dose of ethanol dose-dependently impaired nest building over the initial 24h of withdrawal in genetically segregating Withdrawal Seizure Control (WSC) mice. In two further studies, acute ethanol withdrawal suppressed nest building for up to two days in WSP-1 females. Deficits in nest building from ethanol were limited to the initial 10h of withdrawal in WSR-1 females and to the initial 24h of withdrawal in WSP-1 and WSR-1 males. Effects of ethanol on nest building for up to two days were found in WSP-2 and WSR-2 mice of both sexes. Nest building deficits in female mice from the first replicate could not be explained by a general decrease in locomotor behavior. These results suggest that nest building is a novel behavioral phenotype for indexing the severity of acute ethanol withdrawal, and that genes contributing to this trait differ from those affecting acute withdrawal HIC severity. Published by Elsevier Inc.

  9. The role of salsolinol in alcohol intake and withdrawal.

    PubMed

    Clow, A; Topham, A; Saunders, J B; Murray, R; Sandler, M

    1985-01-01

    We studied the urinary excretion of the tetrahydroisoquinoline (TIQ) salsolinol, formed from acetaldehyde and dopamine, in both severely and moderately dependent alcoholics during withdrawal from alcohol and subsequent challenge with an acute dose of alcohol and L-dopa, and compared these results with controls. Plasma acetaldehyde and alcohol levels in a sub-population of severely dependent withdrawn alcoholic and control subjects following an acute dose of alcohol were also determined. Salsolinol excretion during the first 4 days of alcohol withdrawal was variable but 10 out of 14 alcoholics showed an increasing trend from day 1 to day 3 and 4 of alcohol withdrawal. L-dopa administration raised salsolinol excretion in controls and withdrawn alcoholics to a uniform extent. Loading of the withdrawn alcoholics with an acute dose of alcohol did not cause an increase in urinary salsolinol concentration (despite increased plasma acetaldehyde). Indeed, 24 h following acute alcohol administration, salsolinol excretion rates were depressed in the alcoholics but not in the controls.

  10. IDENTIFICATION AND MANAGEMENT OF ALCOHOL WITHDRAWAL SYNDROME

    PubMed Central

    Mirijello, Antonio; D’Angelo, Cristina; Ferrulli, Anna; Vassallo, Gabriele; Antonelli, Mariangela; Caputo, Fabio; Leggio, Lorenzo; Gasbarrini, Antonio; Addolorato, Giovanni

    2016-01-01

    Symptoms of alcohol withdrawal syndrome may develop within 6–24 hours after the abrupt discontinuation or decrease of alcohol consumption. Symptoms can vary from autonomic hyperactivity and agitation to delirium tremens. The gold-standard treatment for alcohol withdrawal syndrome is represented by benzodiazepines. Among them, different agents (i.e., long-acting or short-acting) and different regimens (front-loading, fixed dose or symptom-triggered) may be chosen on the basis of patient characteristics. Severe withdrawal could require ICU admission and the use of barbiturates or propofol. Other drugs, such as alpha2-agonists (clonidine and dexmetedomidine) and beta-blockers can be used as adjunctive treatments to control neuroautonomic hyperactivity. Furthermore, neuroleptics can help control hallucinations. Finally, other medications for the treatment for alcohol withdrawal syndrome have been investigated with promising results. These include carbamazepine, valproate, sodium oxybate, baclofen, gabapentin, and topiramate. The usefulness of these agents will be discussed in the text. PMID:25666543

  11. Localization of brain 5α-reductase messenger RNA in mice selectively bred for high chronic alcohol withdrawal severity.

    PubMed

    Roselli, Charles E; Finn, Timothy J; Ronnekleiv-Kelly, Sean M; Tanchuck, Michelle A; Kaufman, Katherine R; Finn, Deborah A

    2011-12-01

    Several lines of evidence suggest that fluctuations in endogenous levels of the γ-aminobutyric acid (GABA)ergic neurosteroid allopregnanolone (ALLO) represent one mechanism for regulation of GABAergic inhibitory tone in the brain, with an ultimate impact on behavior. Consistent with this idea, there was an inverse relationship between ALLO levels and symptoms of anxiety and depression in humans and convulsive activity in rodents during alcohol withdrawal. Our recent studies examined the activity and expression of 5α-reductase (Srd5a1), the rate-limiting enzyme in the biosynthesis of ALLO, during alcohol withdrawal in mice selectively bred for high chronic alcohol withdrawal (Withdrawal Seizure-Prone [WSP]) and found that Srd5a1 was downregulated in the cortex and hippocampus over the time course of dependence and withdrawal. The purpose of the present studies was to extend these findings and more discretely map the regions of Srd5a1 expression in mouse brain using radioactive in situ hybridization in WSP mice that were ethanol naïve, following exposure to 72h ethanol vapor (dependent) or during peak withdrawal. In naïve animals, expression of Srd5a1 was widely distributed throughout the mouse brain, with highest expression in specific regions of the cerebral cortex, hippocampus, thalamus, hypothalamus, and amygdala. In dependent animals and during withdrawal, there was no change in Srd5a1 expression in cortex or hippocampus, which differed from our recent findings in dissected tissues. These results suggest that local Srd5a1 mRNA expression in WSP brain may not change in parallel with local ALLO content or withdrawal severity. Published by Elsevier Inc.

  12. Localization of Brain 5α-Reductase Messenger RNA in Mice Selectively Bred for High Chronic Alcohol Withdrawal Severity

    PubMed Central

    Roselli, Charles E.; Finn, Tim J.; Ronnekleiv-Kelly, Sean M.; Tanchuck, Michelle A.; Kaufman, Katherine R.; Finn, Deborah A.

    2011-01-01

    Several lines of evidence suggest that fluctuations in endogenous levels of the γ-aminobutyric acid (GABA)ergic neurosteroid allopregnanolone (ALLO) represent one mechanism for regulation of GABAergic inhibitory tone in the brain, with an ultimate impact on behavior. Consistent with this idea, there was an inverse relationship between ALLO levels and symptoms of anxiety and depression in humans and convulsive activity in rodents during alcohol withdrawal. Our recent studies examined activity and expression of 5α-reductase (Srd5a1), the rate-limiting enzyme in the biosynthesis of ALLO, during alcohol withdrawal in mice selectively bred for high chronic alcohol withdrawal (Withdrawal Seizure-Prone, WSP) and found that Srd5a1 was down-regulated in the cortex and hippocampus over the time course of dependence and withdrawal. The purpose of the present studies was to extend these findings and more discretely map the regions of Srd5a1 expression in mouse brain using radioactive in situ hybridization in WSP mice that were ethanol naïve, following exposure to 72 h ethanol vapor (dependent) or during peak withdrawal. In naïve animals, expression of Srd5a1 was widely distributed throughout the mouse brain, with highest expression in specific regions of the cerebral cortex, hippocampus, thalamus, hypothalamus, and amygdala. In dependent animals and during withdrawal, there was no change in Srd5a1 expression in cortex or hippocampus, which differed from our recent findings in dissected tissues. These results suggest that local Srd5a1 mRNA expression in WSP brain may not change in parallel with local ALLO content or withdrawal severity. PMID:21917407

  13. Inpatient alcohol withdrawal syndrome.

    PubMed

    Monte-Secades, R; Rabuñal-Rey, R; Guerrero-Sande, H

    2015-03-01

    A 55-year-old man was admitted for a femur fracture; an alcohol fetor was noted on admission. The following day, the patient began to experience tremors and nervousness. Intravenous haloperidol was administered. Shortly afterwards, the patient experienced two generalized seizures and then began to experience delirium and uncontrollable agitation. The patient was diagnosed with alcohol withdrawal syndrome; high doses of intravenous midazolam were prescribed and infused. A few hours later, the patient presented signs of respiratory depression, requiring a transfer to the intensive care unit. After a review of the medical history, it was determined that the patient had been admitted on 3 previous occasions due to alcohol withdrawal and had progressed to delirium tremens after experiencing seizures. Can the risk of alcohol withdrawal syndrome and the need for prophylactic treatment be assessed on admission? Were appropriate monitoring and treatment measures employed? Would it have been possible to change his outcome? Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  14. 27 CFR 19.729 - Withdrawal of fuel alcohol.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Withdrawal of fuel alcohol. 19.729 Section 19.729 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU..., Withdrawal, and Transfer of Spirits § 19.729 Withdrawal of fuel alcohol. (a) For each shipment or other...

  15. Improving alcohol withdrawal outcomes in acute care.

    PubMed

    Melson, Jo; Kane, Michelle; Mooney, Ruth; Mcwilliams, James; Horton, Terry

    2014-01-01

    Excessive alcohol consumption is the nation's third leading cause of preventable deaths. If untreated, 6% of alcohol-dependent patients experience alcohol withdrawal, with up to 10% of those experiencing delirium tremens (DT), when they stop drinking. Without routine screening, patients often experience DT without warning. Reduce the incidence of alcohol withdrawal advancing to DT, restraint use, and transfers to the intensive care unit (ICU) in patients with DT. In October 2009, the alcohol withdrawal team instituted a care management guideline used by all disciplines, which included tools for screening, assessment, and symptom management. Data were obtained from existing datasets for three quarters before and four quarters after implementation. Follow-up data were analyzed and showed a great deal of variability in transfers to the ICU and restraint use. Percentage of patients who developed DT showed a downward trend. Incidence of alcohol withdrawal advancing to DT and, in patients with DT, restraint use and transfers to the ICU. Initial data revealed a decrease in percentage of patients with alcohol withdrawal who experienced DT (16.4%-12.9%). In patients with DT, restraint use decreased (60.4%-44.4%) and transfers to the ICU decreased (21.6%-15%). Follow-up data indicated a continued downward trend in patients with DT. Changes were not statistically significant. Restraint use and ICU transfers maintained postimplementation levels initially but returned to preimplementation levels by third quarter 2012. Early identification of patients for potential alcohol withdrawal followed by a standardized treatment protocol using symptom-triggered dosing improved alcohol withdrawal management and outcomes.

  16. 27 CFR 19.729 - Withdrawal of fuel alcohol.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Withdrawal of fuel alcohol..., DEPARTMENT OF THE TREASURY ALCOHOL DISTILLED SPIRITS PLANTS Distilled Spirits for Fuel Use Rules for Use, Withdrawal, and Transfer of Spirits § 19.729 Withdrawal of fuel alcohol. (a) For each shipment or other...

  17. Anticonvulsants for the treatment of alcohol withdrawal syndrome and alcohol use disorders.

    PubMed

    Hammond, Christopher J; Niciu, Mark J; Drew, Shannon; Arias, Albert J

    2015-04-01

    Alcoholic patients suffer from harmful allostatic neuroplastic changes in the brain causing an acute withdrawal syndrome upon cessation of drinking followed by a protracted abstinence syndrome and an increased risk of relapse to heavy drinking. Benzodiazepines have long been the treatment of choice for detoxifying patients and managing alcohol withdrawal syndrome (AWS). Non-benzodiazepine anticonvulsants (NBACs) are increasingly being used both for alcohol withdrawal management and for ongoing outpatient treatment of alcohol dependence, with the goal of either abstinence or harm reduction. This expert narrative review summarizes the scientific basis and clinical evidence supporting the use of NBACs in treating AWS and for reducing harmful drinking patterns. There is less evidence in support of NBAC therapy for AWS, with few placebo-controlled trials. Carbamazepine and gabapentin appear to be the most promising adjunctive treatments for AWS, and they may be useful as monotherapy in select cases, especially in outpatient settings and for the treatment of mild-to-moderate low-risk patients with the AWS. The body of evidence supporting the use of the NBACs for reducing harmful drinking in the outpatient setting is stronger. Topiramate appears to have a robust effect on reducing harmful drinking in alcoholics. Gabapentin is a potentially efficacious treatment for reducing the risk of relapse to harmful drinking patterns in outpatient management of alcoholism. Gabapentin's ease of use, rapid titration, good tolerability, and efficacy in both the withdrawal and chronic phases of treatment make it particularly appealing. In summary, several NBACs appear to be beneficial in treating AWS and alcohol use disorders.

  18. Anticonvulsants for the Treatment of Alcohol Withdrawal Syndrome and Alcohol Use Disorders

    PubMed Central

    Hammond, Christopher J.; Niciu, Mark J.; Drew, Shannon; Arias, Albert J.

    2015-01-01

    Alcoholic patients suffer from harmful allostatic neuroplastic changes in the brain causing an acute withdrawal syndrome upon cessation of drinking followed by a protracted abstinence syndrome and an increased risk of relapse to heavy drinking. Benzodiazepines have long been the treatment of choice for detoxifying patients and managing alcohol withdrawal syndrome (AWS). Non-benzodiazepine anticonvulsants (NBACs) are increasingly being used both for alcohol withdrawal management and for ongoing outpatient treatment of alcohol dependence, with the goal of either abstinence or harm reduction. This expert narrative review summarizes the scientific basis and clinical evidence supporting the use of NBACs in treating AWS and for reducing harmful drinking patterns. There is less evidence in support of NBAC therapy for AWS, with few placebo-controlled trials. Carbamazepine and gabapentin appear to be the most promising adjunctive treatments for AWS, and they may be useful as monotherapy in select cases, especially in outpatient settings and for the treatment of mild-to-moderate low-risk patients with the AWS. The body of evidence supporting the use of the NBACs for reducing harmful drinking in the outpatient setting is stronger. Topiramate appears to have a robust effect on reducing harmful drinking in alcoholics. Gabapentin is a potentially efficacious treatment for reducing the risk of relapse to harmful drinking patterns in outpatient management of alcoholism. Gabapentin's ease of use, rapid titration, good tolerability, and efficacy in both the withdrawal and chronic phases of treatment make it particularly appealing. In summary, several NBACs appear to be beneficial in treating AWS and alcohol use disorders. PMID:25895020

  19. 27 CFR 19.997 - Withdrawal of fuel alcohol.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Withdrawal of fuel alcohol. 19.997 Section 19.997 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... and Transfers § 19.997 Withdrawal of fuel alcohol. For each shipment or other removal of fuel alcohol...

  20. Preparing Nursing and Social Work Students to Care for Patients in Acute Alcohol Withdrawal.

    PubMed

    Gates, Sharon A; Brown, James R

    Alcohol and other drug abuse has become a national crisis with approximately 26% of general medical patients having alcohol-related problems. New nurses and social workers are often not prepared to care for patients with severe alcohol withdrawal symptoms because they lack experience in actual crisis situations. The purpose of this study was to prepare nursing and social work students to care for a patient undergoing an acute alcohol withdrawal process. Nine groups of 8-10 students participated in a 2.5-hour simulation event that included an alcohol withdrawal seizure, team meeting, and discharge of the patient. Students recognized the importance of all the professional roles and how each professional benefits patient care. Before the simulation, students thought they were prepared to care for patients experiencing alcohol withdrawal; however, the crisis of an alcohol seizure decreased the student's ability to perform skills and communicate effectively. These findings suggest that new nurses and social workers may not be prepared to care for the acute alcohol withdrawal patient.

  1. Feasibility and reliability of the SHOT: A short scale for measuring pretreatment severity of alcohol withdrawal in the emergency department.

    PubMed

    Gray, Sara; Borgundvaag, Bjug; Sirvastava, Anita; Randall, Ian; Kahan, Meldon

    2010-10-01

    Use of a symptom-triggered scale to measure the severity of alcohol withdrawal could reduce the rate of seizures and other complications. The current standard scale, the Clinical Institute of Withdrawal Assessment (CIWA), takes a mean (±SD) of 5 minutes to complete, requiring 30 minutes of nursing time per patient when multiple measures are required. The objective was to assess the feasibility and reliability of a brief scale of alcohol withdrawal severity. The SHOT is a brief scale designed to assess alcohol withdrawal in the emergency department (ED). It includes four items: sweating, hallucinations, orientation, and tremor (SHOT). It was developed based on a literature review and a consensus process by emergency and addiction physicians. The SHOT was first piloted in one ED, and then a prospective observational study was conducted at a different ED to measure its feasibility and reliability. Subjects included patients who were in alcohol withdrawal. One nurse administered the SHOT and CIWA, and the physician repeated the SHOT independently. The SHOT was done only at baseline, before treatment was administered. In the pilot study (12 patients), the SHOT took 1 minute to complete on average, and the CIWA took 5 minutes. Sixty-one patients participated in the prospective study. For the SHOT and the CIWA done by the same nurse, the kappa was 0.88 (95% confidence interval [CI] = 0.52 to 1.0; p < 0.0001), and the Pearson's r was 0.71 (p < 0.001). The kappa for the nurse's CIWA score and the physician's SHOT score was 0.61 (95% CI = 0.25 to 0.97; p < 0.0006), and the Pearson's r was 0.48 (p = 0.002). The SHOTs performed by the nurse and physician agreed on the need for benzodiazepine treatment in 30 of 37 cases (82% agreement, kappa = 0.35, 95% CI = 0.03 to 0.67; p < 0.02). The mean (±SD) time taken by nurses and physicians to complete the SHOT was 1 (± 0.52) minute (median = 0.6 minutes). Seventeen percent of patients scored positive on the SHOT for hallucinations

  2. Gut microbiota modulates alcohol withdrawal-induced anxiety in mice.

    PubMed

    Xiao, Hui-Wen; Ge, Chang; Feng, Guo-Xing; Li, Yuan; Luo, Dan; Dong, Jia-Li; Li, Hang; Wang, Haichao; Cui, Ming; Fan, Sai-Jun

    2018-05-01

    Excessive alcohol consumption remains a major public health problem that affects millions of people worldwide. Accumulative experimental evidence has suggested an important involvement of gut microbiota in the modulation of host's immunological and neurological functions. However, it is previously unknown whether enteric microbiota is implicated in the formation of alcohol withdrawal-induced anxiety. Using a murine model of chronic alcoholism and withdrawal, we examined the impact of alcohol consumption on the possible alterations of gut microbiota as well as alcohol withdrawal-induced anxiety and behavior changes. The 16S rRNA sequencing revealed that alcohol consumption did not alter the abundance of bacteria, but markedly changed the composition of gut microbiota. Moreover, the transplantation of enteric microbes from alcohol-fed mice to normal healthy controls remarkably shaped the composition of gut bacteria, and elicited behavioral signs of alcohol withdrawal-induced anxiety. Using quantitative real-time polymerase chain reaction, we further confirmed that the expression of genes implicated in alcohol addiction, BDNF, CRHR1 and OPRM1, was also altered by transplantation of gut microbes from alcohol-exposed donors. Collectively, our findings suggested a possibility that the alterations of gut microbiota composition might contribute to the development of alcohol withdrawal-induced anxiety, and reveal potentially new etiologies for treating alcohol addiction. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

  3. Baclofen for alcohol withdrawal.

    PubMed

    Liu, Jia; Wang, Lu-Ning

    2017-08-20

    Baclofen shows potential for rapidly reducing symptoms of severe alcohol withdrawal syndrome (AWS) in people with alcoholism. Treatment with baclofen is easy to manage and rarely produces euphoria or other pleasant effects, or craving for the drug. This is an updated version of the original Cochrane Review published in 2015, Issue 4. To assess the efficacy and safety of baclofen for people with AWS. We updated our searches of the following databases to March 2017: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, PubMed, Embase, and CINAHL. We also searched registers of ongoing trials. We handsearched the references quoted in the identified trials, and sought information from researchers, pharmaceutical companies, and relevant trial authors about unpublished or uncompleted trials. We placed no restrictions on language. We included all randomised controlled clinical trials (RCTs) evaluating baclofen versus placebo or any other treatment for people with AWS. We excluded uncontrolled, non-randomised, or quasi-randomised trials. We included both parallel group and cross-over studies. We used standard methodological procedures expected by Cochrane. We included three RCTs with 141 randomised participants. We did not perform meta-analyses due to the different control interventions. For the comparison of baclofen and placebo (1 study, 31 participants), there was no significant difference in Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) scores (very low quality evidence). For the comparison of baclofen and diazepam (1 study, 37 participants), there was no significant difference in CIWA-Ar scores (very low quality evidence), adverse events (risk difference (RD) 0.00, 95% confidence interval (CI) -0.10 to 0.10; very low quality evidence), dropouts (RD 0.00, 95% CI -0.10 to 0.10; very low quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI -0.10 to 0.10; very low quality evidence). For the comparison of

  4. Ketogenic Diet Suppresses Alcohol Withdrawal Syndrome in Rats.

    PubMed

    Dencker, Ditte; Molander, Anna; Thomsen, Morgane; Schlumberger, Chantal; Wortwein, Gitta; Weikop, Pia; Benveniste, Helene; Volkow, Nora D; Fink-Jensen, Anders

    2018-02-01

    Alcohol use disorder is underdiagnosed and undertreated, and up to 50% of alcohol-abstinent patients diagnosed with alcohol dependence relapse within the first year of treatment. Current treatments for the maintenance of alcohol abstinence in patients with alcohol use disorder have limited efficacy, and there is an urgent need for novel treatment strategies. Decreased cerebral glucose metabolism and increased brain uptake of acetate were recently reported in heavy drinkers, relative to controls. Given the switch of metabolic fuel from glucose to acetate in the alcohol-dependent brain, we investigated the potential therapeutic benefit of a ketogenic diet in managing alcohol withdrawal symptoms during detoxification. Male Sprague Dawley rats fed either ketogenic or regular diet were administered ethanol or water orally, twice daily for 6 days while the diet conditions were maintained. Abstinence symptoms were rated 6, 24, 48, and 72 hours after the last alcohol administration. Maintenance on a ketogenic diet caused a significant decrease in the alcohol withdrawal symptoms' "rigidity" and "irritability." Our preclinical pilot study suggests that a ketogenic diet may be a novel approach for treating alcohol withdrawal symptoms in humans. Copyright © 2017 by the Research Society on Alcoholism.

  5. Acupuncture for alcohol withdrawal: a randomized controlled trial.

    PubMed

    Trümpler, François; Oez, Suzan; Stähli, Peter; Brenner, Hans Dieter; Jüni, Peter

    2003-01-01

    Previous trials on acupuncture in alcohol addiction were in outpatients and focused on relapse prevention. Rates of dropout were high and interpretation of results difficult. We compared auricular laser and needle acupuncture with sham laser stimulation in reducing the duration of alcohol withdrawal. Inpatients undergoing alcohol withdrawal were randomly allocated to laser acupuncture (n = 17), needle acupuncture (n = 15) or sham laser stimulation (n = 16). Attempts were made to blind patients, therapists and outcome assessors, but this was not feasible for needle acupuncture. The duration of withdrawal symptoms (as assessed using a nurse-rated scale) was the primary outcome; the duration of sedative prescription was the secondary outcome. Patients randomized to laser and sham laser had identical withdrawal symptom durations (median 4 days). Patients randomized to needle stimulation had a shorter duration of withdrawal symptoms (median 3 days; P = 0.019 versus sham intervention), and tended to have a shorter duration of sedative use, but these differences diminished after adjustment for baseline differences. The data from this pilot trial do not suggest a relevant benefit of auricular laser acupuncture for alcohol withdrawal. A larger trial including adequate sham interventions is needed, however, to reliably determine the effectiveness of any type of auricular acupuncture in this condition.

  6. Alcohol withdrawal syndrome: symptom-triggered versus fixed-schedule treatment in an outpatient setting.

    PubMed

    Elholm, Bjarne; Larsen, Klaus; Hornnes, Nete; Zierau, Finn; Becker, Ulrik

    2011-01-01

    To investigate whether, in the treatment with chlordiazepoxide for outpatient alcohol withdrawal, there are advantages of symptom-triggered self-medication over a fixed-schedule regimen. A randomized controlled trial in outpatient clinics for people suffering from alcohol dependence (AD) and alcohol-related problems; 165 adult patients in an outpatient setting in a specialized alcohol treatment unit were randomized 1:1 to either a symptom-triggered self-medication or tapered dose, using chlordiazepoxide. Alcohol withdrawal symptoms, amount of medication, duration of symptoms, time to relapse and patient satisfaction were measured. Patients assessed their symptoms using the Short Alcohol Withdrawal Scale (SAWS). Patient satisfaction was monitored by the Diabetes Treatment Satisfaction Questionnaire. We used the Well-Being Index and the European addiction severity index for the 1-year follow-up. We found no differences in the quantity of medication consumed, time to relapse, well being or treatment satisfaction. Symptom-triggered self-medication was as safe as fixed-schedule medication in treating outpatients with AD and mild to moderate symptoms of AWS. The SAWS is a powerful monitoring tool, because it is brief and permits the subject to log the withdrawal symptoms.

  7. [Alcohol withdrawal syndrome dynamics during treatment with nooclerin (deanoli aceglumas)].

    PubMed

    Agibalova, T V; Buzik, O Zh; Rychkova, O V; Smyshlyaev, A V; Rumbesht, V V

    2018-01-01

    To study the efficacy of nooclerin (deanoli aceglumas) in alcohol withdrawal syndrome assessed by clinical and biochemical characteristics. A multicenter, open, randomized, comparative study of nooclerin in the complex treatment of alcohol withdrawal syndrome included 90 patients. The patients were randomized into nooclerin group (n=55) and control group (n=35). Nooclerin reduced alcohol withdrawal symptoms more significantly throughout the whole study period. There were significant between-group differences on the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) and the Multidimensional Fatigue Inventory (МFI-20). However, patients exhibited no excessive activity. No adverse side-effects were observed.

  8. Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study.

    PubMed

    Rosenson, Jonathan; Clements, Carter; Simon, Barry; Vieaux, Jules; Graffman, Sarah; Vahidnia, Farnaz; Cisse, Bitou; Lam, Joseph; Alter, Harrison

    2013-03-01

    Acute alcohol withdrawal syndrome (AAWS) is encountered in patients presenting acutely to the Emergency Department (ED) and often requires pharmacologic management. We investigated whether a single dose of intravenous (i.v.) phenobarbital combined with a standardized lorazepam-based alcohol withdrawal protocol decreases intensive care unit (ICU) admission in ED patients with acute alcohol withdrawal. This was a prospective, randomized, double-blind, placebo-controlled study. Patients were randomized to receive either a single dose of i.v. phenobarbital (10 mg/kg in 100 mL normal saline) or placebo (100 mL normal saline). All patients were placed on the institutional symptom-guided lorazepam-based alcohol withdrawal protocol. The primary outcome was initial level of hospital admission (ICU vs. telemetry vs. floor ward). There were 198 patients enrolled in the study, and 102 met inclusion criteria for analysis. Fifty-one patients received phenobarbital and 51 received placebo. Baseline characteristics and severity were similar in both groups. Patients that received phenobarbital had fewer ICU admissions (8% vs. 25%, 95% confidence interval 4-32). There were no differences in adverse events. A single dose of i.v. phenobarbital combined with a symptom-guided lorazepam-based alcohol withdrawal protocol resulted in decreased ICU admission and did not cause increased adverse outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. [Treatment of Alcohol Withdrawal Syndrome with Oxazepam or Clomethiazole - A Naturalistic Observational Study].

    PubMed

    Verthein, Uwe; Kuhn, Silke; Gabriel, Katrin; Mautsch, Ulrich; Reimer, Jens; Behrendt, Klaus

    2018-03-01

    Whilst internationally benzodiazepines are first choice for treatment of alcohol withdrawal syndrome, Germany has a long tradition with clomethiazole. This study explores effectiveness of clomethiazole versus oxazepam in the treatment of alcohol withdrawal syndrome within an observational, stratified, non-inferiority study in routine care. Main outcome criterion was severity of the alcohol withdrawal syndrome (Alcohol Withdrawal Syndrome [AWS]) Scale in the first five days. Additionally, the association between the detoxification protocol (five vs. ten days) and AWS-Score was examined. 453 patients (74.2 % male, average age 47.1 years [± 9.2]) took part; 249 received oxazepam (55.0 %) and 204 clomethiazole (45.0 %). The average duration of inpatient treatment was 14.0 days (± 6.3) in both groups. The average AWS-score was lower in the oxazepam group compared to the clomethiazole group (50.0 [± 26.5] vs. 56.2 [± 31.5]; p < .05; effect size d = - .25). Patients with a shorter detoxification protocol had a lower AWS sum score compared to patients with a longer protocol (p < .001; d = - .46). In treatment of alcohol withdrawal syndrome in routine care oxazepam yields at least comparable results to clomethiazole. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Tobacco smoking interferes with GABAA receptor neuroadaptations during prolonged alcohol withdrawal

    PubMed Central

    Cosgrove, Kelly P.; McKay, Reese; Esterlis, Irina; Kloczynski, Tracy; Perkins, Evgenia; Bois, Frederic; Pittman, Brian; Lancaster, Jack; Glahn, David C.; O’Malley, Stephanie; Carson, Richard E.; Krystal, John H.

    2014-01-01

    Understanding the effects of tobacco smoking on neuroadaptations in GABAA receptor levels over alcohol withdrawal will provide critical insights for the treatment of comorbid alcohol and nicotine dependence. We conducted parallel studies in human subjects and nonhuman primates to investigate the differential effects of tobacco smoking and nicotine on changes in GABAA receptor availability during acute and prolonged alcohol withdrawal. We report that alcohol withdrawal with or without concurrent tobacco smoking/nicotine consumption resulted in significant and robust elevations in GABAA receptor levels over the first week of withdrawal. Over prolonged withdrawal, GABAA receptors returned to control levels in alcohol-dependent nonsmokers, but alcohol-dependent smokers had significant and sustained elevations in GABAA receptors that were associated with craving for alcohol and cigarettes. In nonhuman primates, GABAA receptor levels normalized by 1 mo of abstinence in both groups—that is, those that consumed alcohol alone or the combination of alcohol and nicotine. These data suggest that constituents in tobacco smoke other than nicotine block the recovery of GABAA receptor systems during sustained alcohol abstinence, contributing to alcohol relapse and the perpetuation of smoking. PMID:25453062

  11. Evaluation of an Alcohol Withdrawal Protocol and a Preprinted Order Set at a Tertiary Care Hospital

    PubMed Central

    Ng, Karen; Dahri, Karen; Chow, Ivy; Legal, Michael

    2011-01-01

    Background: Alcohol withdrawal protocols involving symptom-triggered administration of benzodiazepine have been established to reduce the duration of treatment and the cumulative benzodiazepine dose (relative to usual care). However, the effects of a protocol combining fixed-schedule and symptom-triggered benzodiazepine dosing are less clear. Objective: To assess the efficacy and safety of a combination fixed-scheduled and symptom-triggered benzodiazepine dosing protocol for alcohol withdrawal, relative to usual care, for medical inpatients at a tertiary care hospital. Methods: A chart review of admissions to the internal medicine service for alcohol withdrawal was conducted to compare treatment outcomes before (October 2005 to April 2007) and after (October 2007 to April 2009) implementation of the combination protocol. The primary outcome was duration of benzodiazepine treatment for alcohol withdrawal. The secondary outcomes were cumulative benzodiazepine dose administered, safety implications, and use of adjunctive medications. Results: A total of 159 patients met the inclusion criteria. Assessable data were available for 71 charts from the pre-implementation period and 72 charts from the post-implementation period. The median duration of benzodiazepine treatment was 91 h before implementation and 57 h after implementation (p < 0.001). Use of the protocol was also associated with a significant reduction in severe complications of alcohol withdrawal (50% versus 33%, p = 0.019), median cumulative benzodiazepine dose (in lorazepam equivalents) (20.0 mg versus 15.5 mg, p = 0.026), and use of adjunctive medications (65% versus 38%, p = 0.001). The incidence of serious adverse outcomes of treatment with benzodiazepines was not significantly different between the 2 groups. Conclusions: Implementation of an alcohol withdrawal protocol with a combination of fixed-schedule and symptom-triggered benzodiazepine dosing in a medical ward was associated with a shorter duration

  12. Levetiracetam for the treatment of alcohol withdrawal syndrome: a multicenter, prospective, randomized, placebo-controlled trial.

    PubMed

    Richter, Christoph; Hinzpeter, Axel; Schmidt, Folkhard; Kienast, Thorsten; Preuss, Ulrich W; Plenge, Thomas; Heinz, Andreas; Schaefer, Martin

    2010-12-01

    Treatment of alcohol withdrawal syndrome (AWS) with benzodiazepines is limited by risk of abuse, intoxication, respiratory problems, and liver toxicity. Alternatives such as carbamazepine and valproate may also have safety problems, such as hepatotoxicity or central nervous adverse effects. We therefore investigated the safety and efficacy of levetiracetam (LV), a newer antiepileptic with a potentially favorable adverse-effect profile, for the treatment of AWS. One hundred six patients were enrolled in a prospective, randomized, double-blind, multicenter, placebo-controlled trial. Levetiracetam was administered in a fixed dose schedule over 6 days. Diazepam was added when symptom triggered as rescue medication. Severity of the AWS was measured with the AWS and Clinical Institute Withdrawal Assessment Scale. Although tolerability and safety data were similar in the LV group when compared with placebo, the total daily and weekly dose of diazepam as rescue medication and the severity of alcohol withdrawal symptoms did not differ significantly between groups. Our data so far do not support an additional effect of LV on the reduction of alcohol withdrawal symptoms.

  13. An alcohol withdrawal test battery measuring multiple behavioral symptoms in mice.

    PubMed

    Metten, Pamela; Schlumbohm, Jason P; Huang, Lawrence C; Greenberg, Gian D; Hack, Wyatt R; Spence, Stephanie E; Crabbe, John C

    2018-05-01

    Despite acceptance that risk for alcohol-use disorder (AUD) has a large genetic component, the identification of genes underlying various components of risk for AUD has been hampered in humans, in part by the heterogeneity of expression of the phenotype. One aspect of AUD is physical dependence. Alcohol withdrawal is a serious consequence of alcohol dependence with multiple symptoms, many of which are seen in multiple species, and can be experienced over a wide-ranging time course. In the present three studies, we developed a battery of withdrawal tests in mice, examining behavioral symptoms from multiple domains that could be measured over time. To permit eventual use of the battery in different strains of mice, we used male and female mice of a genetically heterogeneous stock developed from intercrossing eight inbred strains. Withdrawal symptoms were assessed using commonly used tests after administration of ethanol in vapor for 72 continuous hours. We found significant effects of ethanol withdrawal versus air-breathing controls on nearly all symptoms, spanning 4 days following ethanol vapor inhalation. Withdrawal produced hypothermia, greater neurohyperexcitability (seizures and tremor), anxiety-like behaviors using an apparatus (such as reduced transitions between light and dark compartments), anhedonia (reduced sucrose preference), Straub tail, backward walking, and reductions in activity; however, there were no changes in thermal pain sensitivity, hyper-reactivity to handling, or anxiety-like emergence behaviors in other apparatus. Using these data, we constructed a refined battery of withdrawal tests. Individual differences in severity of withdrawal among different tests were weakly correlated at best. This battery should be useful for identifying genetic influences on particular withdrawal behaviors, which should reflect the influences of different constellations of genes. Published by Elsevier Inc.

  14. Ethosuximide reduces electrographical and behavioral correlates of alcohol withdrawal seizure in DBA/2J mice

    PubMed Central

    Riegle, Melissa A.; Masicampo, Melissa M.; Caulder, Erin H.; Godwin, Dwayne W.

    2015-01-01

    Chronic alcohol abuse depresses the nervous system and, upon cessation, rebound hyperexcitability can result in withdrawal seizure. Withdrawal symptoms, including seizures, may drive individuals to relapse, thus representing a significant barrier to recovery. Our lab previously identified an upregulation of the thalamic T-type calcium (T channel) isoform CaV3.2 as a potential contributor to the generation and propagation of seizures in a model of withdrawal. In the present study, we examined whether ethosuximide (ETX), a T-channel antagonist, could decrease the severity of ethanol withdrawal seizures by evaluating electrographical and behavioral correlates of seizure activity. DBA/2J mice were exposed to an intermittent ethanol exposure paradigm. Mice were treated with saline or ETX in each withdrawal period, and cortical EEG activity was recorded to determine seizure severity. We observed a progression in seizure activity with each successive withdrawal period. Treatment with ETX reduced ethanol withdrawal-induced spike and wave discharges (SWDs), in terms of absolute number, duration of events, and contribution to EEG power reduction in the 6–10 Hz frequency range. We also evaluated the effects of ETX on handling-induced convulsions. Overall, we observed a decrease in handling-induced convulsion severity in mice treated with ETX. Our findings suggest that ETX may be a useful pharmacological agent for studies of alcohol withdrawal and treatment of resulting seizures. PMID:24933286

  15. Algorithm Analysis of the DSM-5 Alcohol Withdrawal Symptom.

    PubMed

    Martin, Christopher S; Vergés, Alvaro; Langenbucher, James W; Littlefield, Andrew; Chung, Tammy; Clark, Duncan B; Sher, Kenneth J

    2018-06-01

    Alcohol withdrawal (AW) is an important clinical and diagnostic feature of alcohol dependence. AW has been found to predict a worsened course of illness in clinical samples, but in some community studies, AW endorsement rates are strikingly high, suggesting false-positive symptom assignments. Little research has examined the validity of the DSM-5 algorithm for AW, which requires either the presence of at least 2 of 8 subcriteria (i.e., autonomic hyperactivity, tremulousness, insomnia, nausea, hallucinations, psychomotor agitation, anxiety, and grand mal seizures), or, the use of alcohol to avoid or relieve these symptoms. We used item and algorithm analyses of data from waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (current drinkers, n = 26,946 at wave 1) to study the validity of DSM-5 AW as operationalized by the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV (AUDADIS-IV). A substantial proportion of individuals given the AW symptom reported only modest to moderate levels of alcohol use and alcohol problems. Alternative AW algorithms were superior to DSM-5 in terms of levels of alcohol use and alcohol problem severity among those with AW, group difference effect sizes, and predictive validity at a 3-year follow-up. The superior alternative algorithms included those that excluded the nausea subcriterion; required withdrawal-related distress or impairment; increased the AW subcriteria threshold from 2 to 3 items; and required tremulousness for AW symptom assignment. The results indicate that the DSM-5 definition of AW, as assessed by the AUDADIS-IV, has low specificity. This shortcoming can be addressed by making the algorithm for symptom assignment more stringent. Copyright © 2018 by the Research Society on Alcoholism.

  16. [Comparison of Two Symptom-Triggered Treatments for Alcohol Withdrawal: HAES vs. SAB-P].

    PubMed

    Holzbach, R; Ihlow, C; Takla, T; Kemper, U; Naber, D

    2016-02-01

    For alcohol withdrawal during hospitalization, often a medication as means for withdrawal needs to be chosen. Modern, score-controlled processes that can be used by the nursing staff after instruction by physicians are frequently not used and even unknown in hospitals. One reason for this is that some of the scores require checking several criteria and are therefore more time-consuming and complicated than use of a fixed-dosage strategy. The SAB-P and HAES are short with only 6 items that can be checked by the nursing staff. Safety of the Hamburg Alcohol Withdrawal Scale (Hamburger Alkoholentzugs-Skala (HAES)) was analyzed retrospectively and prospectively with regard to score-controlled alcohol-withdrawal treatment after rating by the nurse staff (Scoregesteuerte Alkoholentzugsbehandlung nach Rating durch das Pflegepersonal (SAB-P)). Incidence of complications in patients treated with SAB-P and HAES was nearly similar with 1% start of delirium and 3% seizures (SAB-P) and 0.5 to 1.5% start of delirium and 0 to 0.5% seizures in the HAES group. With both scales it was possible to start medical treatment while still under falling alcohol levels (0.93 and 0.91%, respectively). Medication dosage was initially higher using the HAES, so that the time needed to monitor withdrawal symptoms could be reduced (3.8 vs. 3.1 days). Using a score-controlled strategy for alcohol withdrawal leads to a lower complication rate than found in literature. The structured procedure was helpful for the nursing staff as well as for the physicians. SAB-P as well as HAES made withdrawal for the patients more comfortable and led to fewer complaints. Because of rapid reaction and faster symptom reduction of HAES, there was less time necessary for monitoring. Simple handling, clomethiazol, oxazepam or diazepam as applicable medication and clear documentation are the advantages of HAES. © Georg Thieme Verlag KG Stuttgart · New York.

  17. AST: A Simplified 3-item Tool for Managing Alcohol Withdrawal.

    PubMed

    Holzman, Samuel B; Rastegar, Darius A

    2016-01-01

    This study compared the Glasgow Modified Alcohol Withdrawal Scale (GMAWS) and a newly devised 3-item "Anxiety Sweats Tremor" Scale (AST) to the Revised Clinical Institute Withdrawal Assessment Scale (CIWA-Ar)-the standard of care for symptom-triggered management of alcohol withdrawal syndrome. Our study took place over 2 separate 1-week observational periods, and included 332 serial evaluations from 85 unique patients. All study participants were treated per hospital protocol based on CIWA-Ar, with supplemental scoring initially by GMAWS and later by AST in tandem. Internal consistency, interitem correlation, and operational characteristics were explored. Median CIWA-Ar score across both phases was 6 (range 0-13), with a median GMAWS score of 2 (range 0-5) and an AST score of 3 (range 0-7). The internal consistency of CIWA-Ar and GMAWS were both poor, with Cronbach alpha scores of 0.46 (n = 156) and 0.41 (n = 156), respectively. The internal consistency of the AST scale was significantly better, with a Cronbach alpha of 0.68 (n = 176). AST identified individuals with CIWA-Ar ≥8 with an area under the receiver-operating characteristic curve of 0.83 (95% confidence interval 0.77-0.89), compared with 0.81 (95% confidence interval 0.74-0.88) for GMAWS. An AST score of ≥3 (out of a possible 9) predicted CIWA-Ar ≥8, with a sensitivity of 93% and a specificity of 63%, whereas the GMAWS had a sensitivity and specificity of 100% and 12%, respectively, based on previously defined cut-offs. A simple 3-item scale demonstrated good internal consistency and reliably identified individuals experiencing significant alcohol withdrawal. This scale needs to be tested in other settings and among patients with a broader spectrum of withdrawal severity.

  18. Social transfer of alcohol withdrawal-induced hyperalgesia in female prairie voles.

    PubMed

    Walcott, Andre T; Smith, Monique L; Loftis, Jennifer M; Ryabinin, Andrey E

    2018-03-27

    The expression of pain serves as a way for animals to communicate potential dangers to nearby conspecifics. Recent research demonstrated that mice undergoing alcohol or morphine withdrawal, or inflammation, could socially communicate their hyperalgesia to nearby mice. However, it is unknown whether such social transfer of hyperalgesia can be observed in other species of rodents. Therefore, the present study investigated if the social transfer of hyperalgesia occurs in the highly social prairie vole (Microtus ochrogaster). We observe that adult female prairie voles undergoing withdrawal from voluntary two-bottle choice alcohol drinking display an increase in nociception. This alcohol withdrawal-induced hypersensitiity is socially transferred to female siblings within the same cage and female strangers housed in separate cages within the same room. These experiments reveal that the social transfer of pain phenomenon is not specific to inbred mouse strains and that prairie voles display alcohol withdrawal and social transfer-induced hyperalgesia.

  19. Combining the audit questionnaire and biochemical markers to assess alcohol use and risk of alcohol withdrawal in medical inpatients.

    PubMed

    Dolman, Jonathan M; Hawkes, Neil D

    2005-01-01

    Alcohol consumption is often under-reported in patients admitted to general hospitals with acute illness. For alcohol-dependent individuals hospital admission results in an enforced period of abstinence with potential alcohol withdrawal symptoms, and possible life threatening complications. Early detection of alcohol use is therefore beneficial to patients and health services. The purpose of this study was to investigate the performance of the alcohol use disorders identification test (AUDIT) questionnaire in the acute medical setting, and the effect of combining routine biological markers-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, and mean corpuscular volume (MCV) on its performance in the early identification of in-patients with alcohol use disorders and at risk of developing symptoms of alcohol withdrawal. Prospective study in consecutive patients admitted to an acute medical admissions ward. All patients were screened using the AUDIT questionnaire and routine blood tests. Patients were then monitored for symptoms of withdrawal using clinical institute withdrawal assessment for alcohol (CIWA-Ar). Of the 874 patients screened using the AUDIT, 98 (11%) screened positive of whom 17 (2% of the 874) experienced clinically significant alcohol withdrawal symptoms, when using serial CIWA-Ar. The AUDIT and serial CIWA-Ar detected all patients who went on to manifest acute withdrawal symptoms. There was no loss of sensitivity at an AUDIT cut-off of 13 or more compared with the lower cut-off of 8 or more. A positive predictive value of 17.3% for an AUDIT score of 8 or more in the detection of withdrawal, increased to 47.1% when found in combination with at least two abnormal biological markers whilst maintaining a sensitivity of 94.1% and specificity of 97.9%. These findings confirm that AUDIT is a useful alcohol screen in general medical settings and that its ability to correctly predict which patients will experience alcohol withdrawal is

  20. Alcohol withdrawal management in adult patients in a high acuity medical surgical transitional care unit: a best practice implementation project.

    PubMed

    Sukhenko, Olga

    2016-01-15

    Excessive alcohol consumption, a major health problem worldwide, affects about 6% of the United States population. Caring for patients with alcohol withdrawal syndrome in a hospital ward presents complex physiologic and psycho-social challenges which are best met with evidence-based practices. An academic medical center in the United States has been experiencing an increase in patients with alcohol withdrawal syndrome. However, gaps in clinician knowledge and infrastructure supporting the management of these patients still existed. The aim of this project was to improve the continuity of care of patients undergoing alcohol withdrawal in a medical surgical high acuity transitional care unit by incorporating evidence-based practices, and thereby to positively impact on patient outcomes. Specific objectives were related to standardized assessments and pharmacologic management strategies. The project used the Joanna Briggs Institute's Practical Application of Clinical Evidence System and Getting Research into Practice audit tool for promoting change in health practice. A baseline clinical audit was conducted to assess compliance with best practices for managing alcohol withdrawal syndrome, which was followed by several interventions targeted at nurses and providers. A follow-up audit was conducted to assess compliance with the implemented strategies. The follow-up audit used the same evidence-based audit criteria as those used for the baseline audit. A non-probabilistic, convenience sampling approach was used. A sample size of 15 patients was used for both the baseline and follow-up audits. The baseline audit revealed a high compliance rate for four of the five audit criteria concerning risk assessment and pharmacologic strategies. There was sub-optimal compliance (53%) with the criterion regarding use of the Clinical Institute Withdrawal Assessment of Alcohol Scale (revised) (CIWA-Ar) scale to assess patients with alcohol withdrawal. After the interventions were

  1. Nest building is a novel method for indexing severity of alcohol withdrawal in mice.

    PubMed

    Greenberg, G D; Huang, L C; Spence, S E; Schlumbohm, J P; Metten, P; Ozburn, A R; Crabbe, J C

    2016-04-01

    Withdrawal after chronic ethanol (EtOH) affects body temperature, goal-directed behavior and motor function in mice and increases general central nervous system excitability. Nest-building tests have been used to assay these states but to this point have not been employed as measures of EtOH withdrawal severity. We first refined nest-scoring methods using a genetically heterogeneous stock of mice (HS/Npt). Mice were then made physically dependent following three days of chronic EtOH vapor inhalation to produce average blood EtOH concentrations (BECs) of 1.89 mg/mL. EtOH withdrawal affected the progression of nest building over time when mice were tested 2-4 days after removal from three days of chronic exposure to EtOH. In a separate group of mice, chronic EtOH vapor inhalation (BECs 1.84 mg/mL) suppressed nest building over days 1-2 but not days 2-3 of withdrawal. In a following experiment, EtOH withdrawal dose-dependently slowed recovery of nest building for up to 32 h. Finally, we determined that long-lasting nest-building deficits extend to mice undergoing withdrawal from a high dose (4 g/kg) of acute EtOH. Sex differences for nest building were absent following EtOH exposure. In mice naïve to EtOH treatments, male mice had lower pre-test body temperatures and increased nest scores across a two-day testing period compared to females. These results suggest that nest building can be used to assess chronic and acute EtOH withdrawal severity in mice. Published by Elsevier B.V.

  2. Environmental enrichment may protect against neural and behavioural damage caused by withdrawal from chronic alcohol intake.

    PubMed

    Nobre, Manoel Jorge

    2016-12-01

    Exposure to stress and prolonged exposure to alcohol leads to neuronal damages in several brain regions, being the medial prefrontal cortex (mPFC) one of the most affected. These changes presumably reduce the ability of the organism to cope with these stimuli and may underlie a series of maladaptive behaviours among which include drug addiction and withdrawal. Drug-addicted individuals show a pattern of behavior similar to patients with lesions of the mPFC. This impairment in the decision-making could be one of the mechanisms responsible for the transition from the casual to compulsive drug use. The environmental enrichment (EE) has a protective effect on the neural and cognitive impairments induced by psychoactive drugs, including ethyl alcohol. The present study aims to determine the influence of withdrawal from intermittent long-term alcohol exposure on alcohol preference, emotional reactivity and neural aspects of early isolated or grouped reared rats kept under standard or complex environments and the influence of social isolation on these measures, as well. Our results point out new insights on this matter showing that the EE can attenuate the adverse effects of withdrawal and social isolation on rat's behavior. This effect is probably due to its protective action on the mPFC integrity, including the cingulate area 1 (Cg1), and the prelimbic (PrL) and infralimbic cortex (IL), what could account for the absence of changes in the emotional reactivity in EE alcohol withdrawal rats. We argue that morphological changes at these cortical levels can afford the emotional, cognitive and behavioural dysregulations verified following withdrawal from chronic alcohol intake. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

  3. Acute withdrawal, protracted abstinence and negative affect in alcoholism: Are they linked?

    PubMed Central

    Heilig, M.; Egli, M.; Crabbe, J.C.; Becker, H.C.

    2012-01-01

    The role of withdrawal-related phenomena in development and maintenance of alcohol addiction remains under debate. A “self-medication” framework postulates that emotional changes are induced by a history of alcohol use, persist into abstinence, and are a major factor in maintaining alcoholism. This view initially focused on negative emotional states during early withdrawal: these are pronounced, occur in the vast majority of alcohol dependent patients, and are characterized by depressed mood and elevated anxiety. This concept lost popularity with the realization that, in most patients, these symptoms abate over 3 – 6 weeks of abstinence, while relapse risk persists long beyond this period. More recently, animal data have established that a prolonged history of alcohol dependence induces more subtle neuroadaptations. These confer altered emotional processing that persists long into protracted abstinence. The resulting behavioral phenotype is characterized by excessive voluntary alcohol intake and increased behavioral sensitivity to stress. Emerging human data support the clinical relevance of negative emotionality for protracted abstinence and relapse. These developments prompt a series of research questions: 1) Are processes observed during acute withdrawal, while transient in nature, mechanistically related to those that remain during protracted abstinence? 2) Is susceptibility to negative emotionality in acute withdrawal in part due to heritable factors, similar to what animal models have indicated for susceptibility to physical aspects of withdrawal? 3) To what extent is susceptibility to negative affect that persists into protracted abstinence heritable? PMID:20148778

  4. Acamprosate attenuates the handling induced convulsions during alcohol withdrawal in Swiss Webster mice

    PubMed Central

    Farook, Justin M.; Krazem, Ali; Littleton, John M.; Barron, Susan

    2008-01-01

    In the present study, we examined the effects of acamprosate for its ability to reduce handling induced convulsions (HICs) during alcohol withdrawal. Diazepam was used as a positive control. Swiss Webster male mice received three daily IP injections of alcohol (2.5 g/kg) or alcohol (2.5 g/kg) + methylpyrazole (4-MP) (9 mg/kg). (4-MP, being an alcohol dehydrogenase inhibitor slows down the breakdown of alcohol. 4-MP in combination with alcohol exhibits a dramatic increase in blood alcohol level compared to alcohol alone). Ten hours following the last alcohol injection, the mice were picked up by the tail and examined for their seizure susceptibility (HICs). Diazepam, a benzodiazepine known to reduce seizures during alcohol withdrawal, significantly reduced these HICs at doses of 0.25, 0.5 and 1mg/kg (p’s < 0.001). Acamprosate, an anti-relapse compound used clinically in newly abstinent alcoholics, also reduced these HICs at doses of 100, 200 and 300mg/kg (p’s < 0.05). This study supports the use of acamprosate during periods of alcohol withdrawal as well as during abstinence. PMID:18577392

  5. Activation of brain NOP receptors attenuates acute and protracted alcohol withdrawal symptoms in the rat.

    PubMed

    Economidou, Daina; Cippitelli, Andrea; Stopponi, Serena; Braconi, Simone; Clementi, Stefano; Ubaldi, Massimo; Martin-Fardon, Rèmi; Weiss, Friedbert; Massi, Maurizio; Ciccocioppo, Roberto

    2011-04-01

    Alcohol withdrawal refers to a cluster of symptoms that may occur from suddenly ceasing the use of alcohol after chronic or prolonged ingestion. These symptoms make alcohol abstinence difficult and increase the risk of relapse in recovering alcoholics. In previous studies, we demonstrated that treatment with Nociceptin/orphanin FQ (N/OFQ) significantly reduces alcohol consumption and attenuates alcohol-seeking behavior induced by environmental conditioning factors or by stress in rats. In this study, we evaluated whether activation of brain NOP receptors may also attenuate alcohol withdrawal signs in rats. For this purpose, animals were subjected to a 6-day chronic alcohol intoxication (by intragastric administration), and at 8, 10, and 12 hours following cessation of alcohol exposure, they were treated intracerebroventricularly (ICV) with N/OFQ (0.0, 1.0, and 3.0 μg/rat). Somatic withdrawal signs were scored after ICV treatment. In a subsequent experiment, to evaluate N/OFQ effects on alcohol withdrawal-induced anxiety, another group of rats was subjected to ethanol intoxication and after 1 week was tested for anxiety behavior in the elevated plus maze (EPM). In the last experiment, an additional group of rats was tested for anxiety elicited by acute ethanol intoxication (hangover anxiety). For this purpose, animals received an acute dose (3.0 g/kg) of 20% alcohol and 12 hour later were tested in the EPM following ICV N/OFQ (0.0, 1.0, and 2.0 μg/rat). Results showed that N/OFQ significantly reduced the expression of somatic withdrawal signs and reversed anxiety-like behaviors associated with both chronic and acute alcohol intoxication. N/OFQ did not affect anxiety scores in nondependent animals. These findings suggest that the N/OFQ-NOP receptor system may represent a promising target for the development of new treatments to ameliorate alcohol withdrawal symptoms. Copyright © 2011 by the Research Society on Alcoholism.

  6. Standardized Passiflora incarnata L. Extract Reverts the Analgesia Induced by Alcohol Withdrawal in Rats.

    PubMed

    Schunck, Rebeca Vargas Antunes; Macedo, Isabel Cristina; Laste, Gabriela; de Souza, Andressa; Valle, Marina Tuerlinckx Costa; Salomón, Janaína L O; Nunes, Ellen Almeida; Campos, Andreia Cristina Wildner; Gnoatto, Simone Cristina Baggio; Bergold, Ana Maria; Konrath, Eduardo L; Dallegrave, Eliane; Arbo, Marcelo Dutra; Torres, Iraci L S; Leal, Mirna Bainy

    2017-08-01

    Passiflora incarnata L. (Passifloraceae) has been traditionally used for treatment of anxiety, insomnia, drug addiction, mild infections, and pain. The aim of this study was to investigate the effect of a commercial extract of P. incarnata in the analgesia induced by alcohol withdrawal syndrome in rats. In addition, brain-derived neurotrophic factor and interleukin-10 levels were evaluated in prefrontal cortex, brainstem, and hippocampus. Male adult rats received by oral gavage: (1: water group) water for 19 days, 1 day interval and water (8 days); (2: P. incarnata group) water for 19 days, 1 day interval and P. incarnata 200 mg/kg (8 days); (3: alcohol withdrawal group) alcohol for 19 days, 1 day interval and water (8 days); and (4: P. incarnata in alcohol withdrawal) alcohol for 19 days, 1 day interval and P. incarnata 200 mg/kg (8 days). The tail-flick and hot plate tests were used as nociceptive response measures. Confirming previous study of our group, it was showed that alcohol-treated groups presented an increase in the nociceptive thresholds after alcohol withdrawal, which was reverted by P. incarnata, measured by the hot plate test. Besides, alcohol treatment increased brain-derived neurotrophic factor and interleukin-10 levels in prefrontal cortex, which was not reverted by P. incarnata. Considering these results, the P. incarnata treatment might be a potential therapy in the alcohol withdrawal syndrome. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Taurine restores the exploratory behavior following alcohol withdrawal and decreases BDNF mRNA expression in the frontal cortex of chronic alcohol-treated rats.

    PubMed

    Hansen, Alana Witt; Almeida, Felipe Borges; Bandiera, Solange; Pulcinelli, Rianne Remus; Fragoso, Ana Luiza Rodrigues; Schneider, Ricardo; Barros, Helena Maria Tannhauser; Gomez, Rosane

    2017-10-01

    Alcohol use disorder is an alarming health problem, and the withdrawal symptoms increase the risk of relapse. We have hypothesized that taurine, a multitarget substance acting as a gamma-aminobutyric acid A receptor (GABA A R) positive modulator and a partial inhibitor of N-methyl-d-aspartate (NMDA) glutamate receptors, may reduce the withdrawal symptoms or modify behaviors when combined with alcohol. Therefore, we investigated the effects of taurine on behavior in the open field test (OFT), the GABA A R α 2 subunit and BDNF mRNA expression in the frontal cortex of rats after chronic alcohol treatment or upon withdrawal. Rats received alcohol 2g/kg (alcohol and withdrawal groups) or water (control group) twice daily by oral gavage for 28days. On day 29, the withdrawal rats received water instead of alcohol, and all groups were reallocated to receive 100mg/kg taurine or vehicle intraperitoneally, once a day for 5days. On day 33, the rats were exposed to OFT; 18h later, they were euthanized, and the frontal cortex was dissected for GABA A R α 2 subunit detection and BDNF mRNA expression determination by real-time quantitative PCR. Taurine administration restored rearing behavior to the control levels in the withdrawal rats. Taurine also showed anxiolytic-like effects in control rats and did not change the behaviors in the chronic alcohol group. Chronic alcohol treatment or withdrawal did not change the GABA A R α 2 subunit or BDNF mRNA expression in the frontal cortex, but taurine decreased the α 2 subunit level in control rats and to the BDNF levels in the alcohol rat group. We conclude that taurine restored exploratory behavior after alcohol withdrawal but that this effect was not related to the GABA A R α 2 subunit or BDNF mRNA expression in the frontal cortex of the rats. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Evaluation of the appropriate use of a CIWA-Ar alcohol withdrawal protocol in the general hospital setting.

    PubMed

    Eloma, Amanda S; Tucciarone, Jason M; Hayes, Edmund M; Bronson, Brian D

    2018-01-01

    The Clinical Institute Withdrawal Assessment-Alcohol, Revised (CIWA-Ar) is an assessment tool used to quantify alcohol withdrawal syndrome (AWS) severity and inform benzodiazepine treatment for alcohol withdrawal. To evaluate the prescribing patterns and appropriate use of the CIWA-Ar protocol in a general hospital setting, as determined by the presence or absence of documented AWS risk factors, patients' ability to communicate, and provider awareness of the CIWA-Ar order. This retrospective chart review included 118 encounters of hospitalized patients placed on a CIWA-Ar protocol during one year. The following data were collected for each encounter: patient demographics, admitting diagnosis, ability to communicate, and admission blood alcohol level; and medical specialty of the clinician ordering CIWA-Ar, documentation of the presence or absence of established AWS risk factors, specific parameters of the protocol ordered, service admitted to, provider documentation of awareness of the active protocol within 48 h of initial order, total benzodiazepine dose equivalents administered and associated adverse events. 57% of patients who started on a CIWA-Ar protocol had either zero or one documented risk factor for AWS (19% and 38% respectively). 20% had no documentation of recent alcohol use. 14% were unable to communicate. 19% of medical records lacked documentation of provider awareness of the ordered protocol. Benzodiazepine associated adverse events were documented in 15% of encounters. The judicious use of CIWA-Ar protocols in general hospitals requires mechanisms to ensure assessment of validated alcohol withdrawal risk factors, exclusion of patients who cannot communicate, and continuity of care during transitions.

  9. Infant emotional withdrawal: a precursor of affective and cognitive disturbance in fetal alcohol spectrum disorders.

    PubMed

    Molteno, Christopher D; Jacobson, Joseph L; Carter, R Colin; Dodge, Neil C; Jacobson, Sandra W

    2014-02-01

    Our aim was to test the hypothesis that emotional withdrawal is an early indicator of affective disorder in infants heavily exposed prenatally to alcohol, which is independent of alcohol-related effects on mother-infant interaction and temperament and discriminated between children later diagnosed with fetal alcohol syndrome (FAS) and partial FAS (PFAS) and predicted cognitive and affective outcomes at 5 and 9 years. The sample consisted of Cape Coloured (mixed ancestry) infants, whose mothers were interviewed during pregnancy regarding their alcohol consumption using a timeline follow-back approach. Infant emotional withdrawal (n = 85) was assessed on the Alarm Distress Baby Scale at 6.5 months. Mother-infant interaction was evaluated from video recordings during free play and infant feeding at 6.5 months (n = 127). Infant temperament was assessed by maternal report on the EAS Temperament Survey at 13 months (n = 119). Sociodemographic and psychological correlates of maternal alcohol use and infant iron deficiency were examined as potential confounders. The children were diagnosed for FAS/PFAS by expert dysmorphologists at 5 years, cognitive and affective function at 5 and 9 years. Prenatal alcohol exposure was associated with increased infant emotional withdrawal and decreased activity, but unrelated to mother-infant interaction or any other temperament measures. Children later diagnosed with FAS and PFAS at 5 years exhibited more emotional withdrawal and less responsivity and activity as infants. Infant withdrawal, responsivity, quality of interaction, and maternal sensitivity also predicted poorer IQ and affective response at 5 and 9 years. When all 4 infant affective measures were examined simultaneously in a regression analysis, only infant emotional withdrawal persisted as a significant predictor of 9-year IQ. This study is the first to document a direct effect of fetal alcohol exposure on emotional withdrawal in infancy. These data link

  10. Comparison of enteral ethanol and benzodiazepines for alcohol withdrawal in neurocritical care patients.

    PubMed

    Gipson, Gregory; Tran, Kim; Hoang, Cuong; Treggiari, Miriam

    2016-09-01

    We designed a study to evaluate the use of benzodiazepines and ethanol in patients being assessed for alcohol withdrawal and compare outcomes between the two agents. This is a retrospective chart review of patients admitted to neurocritical care or neurosurgical services who were at risk for ethanol withdrawal between June 2011 and September 2015. Patients were divided into two groups based on the first medication administered for alcohol withdrawal management, either benzodiazepine (n=50) or enteral ethanol (n=50). The primary endpoint was the maximum change in Clinical Institute Withdrawal Assessment of Alcohol scale (CIWA) score within the first 24hours. Secondary endpoints included maximum and minimum CIWA score in 5days, length of stay, and change in Glasgow Coma Scale. Study groups differed by mortality risk, level of coma at admission, and other clinical characteristics, with the ethanol group appearing less severely ill. There was no significant difference between the two groups in the maximum change in CIWA score at 24hours (-0.97, 95%CI: -3.21 to 1.27, p=0.39). Hospital and intensive care unit length of stay was 6.5 days and 1 day shorter for the ethanol group (p=0.03 and p=0.02, respectively). In summary, enteral ethanol was preferentially used in patients who are more likely to be capable of tolerating oral intake. We found that the change from baseline in CIWA score or other physiologic variables was not substantially different between the two agents. The overall utility of benzodiazepines and enteral ethanol remains unclear for this population and further study is needed to determine superiority. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Association of testosterone and BDNF serum levels with craving during alcohol withdrawal.

    PubMed

    Heberlein, Annemarie; Lenz, Bernd; Opfermann, Birgitt; Gröschl, Michael; Janke, Eva; Stange, Katrin; Groh, Adrian; Kornhuber, Johannes; Frieling, Helge; Bleich, Stefan; Hillemacher, Thomas

    2016-08-01

    Preclinical and clinical studies show associations between testosterone and brain-derived neurotrophic growth factor (BDNF) serum levels. BDNF and testosterone have been independently reported to influence alcohol consumption. Therefore, we aimed to investigate a possible interplay of testosterone and BDNF contributing to alcohol dependence. Regarding possible interplay of testosterone and BDNF and the activity of the hypothalamic pituitary axis (HPA), we included cortisol serum levels in our research. We investigated testosterone and BDNF serum levels in a sample of 99 male alcohol-dependent patients during alcohol withdrawal (day 1, 7, and 14) and compared them to a healthy male control group (n = 17). The testosterone serum levels were significantly (p < 0.001) higher in the patients' group than in the control group and decreased significantly during alcohol withdrawal (p < 0.001). The decrease of testosterone serum levels during alcohol withdrawal (days 1-7) was significantly associated with the BDNF serum levels (day 1: p = 0.008). In a subgroup of patients showing high cortisol serum levels (putatively mirroring high HPA activity), we found a significant association of BDNF and testosterone as well as with alcohol craving measured by the Obsessive and Compulsive Drinking Scale (OCDS). Our data suggest a possible association of BDNF and testosterone serum levels, which may be relevant for the symptomatology of alcohol dependence. Further studies are needed to clarify our results. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. INFANT EMOTIONAL WITHDRAWAL: A PRECURSOR OF AFFECTIVE AND COGNITIVE DISTURBANCE IN FETAL ALCOHOL SPECTRUM DISORDERS

    PubMed Central

    Molteno, Christopher D.; Jacobson, Joseph L.; Carter, R. Colin; Dodge, Neil C.; Jacobson, Sandra W.

    2013-01-01

    Objectives To test the hypothesis that emotional withdrawal is an early indicator of affective disorder in infants heavily exposed prenatally to alcohol, which is independent of alcohol-related effects on mother-infant interaction and temperament and discriminated between children later diagnosed with fetal alcohol syndrome (FAS) and partial FAS (PFAS) and predicted cognitive and affective outcomes at 5 and 9 years. Methods The sample consisted of Cape Coloured (mixed ancestry) infants, whose mothers were interviewed during pregnancy regarding their alcohol consumption using a timeline follow-back approach. Infant emotional withdrawal (n = 85) was assessed on the Alarm Distress Baby Scale at 6.5 months. Mother-infant interaction was evaluated from video recordings during free play and infant feeding at 6.5 months (n = 127). Infant temperament was assessed by maternal report on the EAS Temperament Survey at 13 months (n = 119). Socio-demographic and psychological correlates of maternal alcohol use and infant iron deficiency were examined as potential confounders. The children were diagnosed for FAS/PFAS by expert dysmorphologists at 5 years; cognitive and affective function, at 5 and 9 years. Results Prenatal alcohol exposure was associated with increased infant emotional withdrawal and decreased activity, but unrelated to mother-infant interaction or any other temperament measures. Children later diagnosed with FAS and PFAS at 5 years exhibited more emotional withdrawal and less responsivity and activity as infants. Infant withdrawal, responsivity, quality of interaction, and maternal sensitivity also predicted poorer IQ and affective response at 5 and 9 years. When all four infant affective measures were examined simultaneously in a regression analysis, only infant emotional withdrawal persisted as a significant predictor of 9-year IQ. Conclusions This study is the first to document a direct effect of fetal alcohol exposure on emotional withdrawal in infancy

  13. Effects of a GABA-ergic medication combination and initial alcohol withdrawal severity on cue-elicited brain activation among treatment-seeking alcoholics.

    PubMed

    Schacht, Joseph P; Anton, Raymond F; Randall, Patrick K; Li, Xingbao; Henderson, Scott; Myrick, Hugh

    2013-06-01

    Many studies have reported medication effects on alcohol cue-elicited brain activation or associations between such activation and subsequent drinking. However, few have combined the methodological rigor of a randomized clinical trial (RCT) with follow-up assessments to determine whether cue-elicited activation predicts relapse during treatment, the crux of alcoholism. This study analyzed functional magnetic resonance imaging (fMRI) data from 48 alcohol-dependent subjects enrolled in a 6-week RCT of an investigational pharmacotherapy. Subjects were randomized, based on their level of alcohol withdrawal (AW) at study entry, to receive either a combination of gabapentin (GBP; up to 1,200 mg for 39 days) and flumazenil (FMZ) infusions (2 days) or two placebos. Midway through the RCT, subjects were administered an fMRI alcohol cue reactivity task. There were no main effects of medication or initial AW status on cue-elicited activation, but these factors interacted, such that the GBP/FMZ/higher AW and placebo/lower AW groups, which had previously been shown to have relatively reduced drinking, demonstrated greater dorsal anterior cingulate cortex (dACC) activation to alcohol cues. Further analysis suggested that this finding represented differences in task-related deactivation and was associated with greater control over alcohol-related thoughts. Among study completers, regardless of medication or AW status, greater left dorsolateral prefrontal cortex (DLPFC) activation predicted more post-scan heavy drinking. These data suggest that alterations in task-related deactivation of dACC, a component of the default mode network, may predict better alcohol treatment response, while activation of DLPFC, an area associated with selective attention, may predict relapse drinking.

  14. [Evaluation of selected socioeconomic factors in patients with acute ethanol intoxication and alcohol withdrawal syndrome].

    PubMed

    Lukasik-Głębocka, Magdalena; Sommerfeld, Karina

    2014-01-01

    Ethanol is commonly overused psychoactive substance in Poland and all around the world. It causes addiction, which occurs as a result of its chronic administration. One of the main symptoms of addiction is hunger due to psychoactive substance that prevents interruption of its adoption and contributes to relapse drinking. Acute poisoning with ethyl alcohol and alcohol withdrawal syndrome are diseases causing a potential danger to life. The prevalence of use and abuse of alcoholic beverages is a potential risk, causing health problems, including permanent damage of the central and peripheral nervous system and socio-economic problems. The aim of this study is to analyze certain aspects of the socio-economic situation of the patients hospitalized in the Department of Toxicology in Raszeja City Hospital in Poznan due to acute ethanol intoxication or alcohol withdrawal syndrome in 2010. 299 patients history was evaluated, among which 161 were treated for acute intoxication with ethanol and 138 due to alcohol withdrawal syndrome. Objects of interest were elements of subjective tests including: marital status of patients, their education and professional activity and the problem of homelessness. The study group consisted of 299 patients in age from 16 to 77 years, hospitalized in the Department of Toxicology in Raszeja City Hospital in Poznan due to acute ethanol intoxication or alcohol withdrawal syndrome. It was found that the largest group consisted of patients remaining married (42.81%) and unmarried (30.43%). Alcohol abuse affects people of all levels of education. In the present study, most patients had a vocational education (37.79%) and medium (23.08%). Patients were analyzed in terms of economic activity, among which about 40% were unemployed. In the whole group more than 10% of those were homeless. Ethyl alcohol intoxication and alcohol withdrawal represents a significant hazard. As a result of reliance, patients lose control of alcohol consumption and they

  15. Adjunct Ketamine Use in the Management of Severe Ethanol Withdrawal.

    PubMed

    Pizon, Anthony F; Lynch, Michael J; Benedict, Neal J; Yanta, Joseph H; Frisch, Adam; Menke, Nathan B; Swartzentruber, Greg S; King, Andrew M; Abesamis, Michael G; Kane-Gill, Sandra L

    2018-05-08

    Ketamine offers a plausible mechanism with favorable kinetics in treatment of severe ethanol withdrawal. The purpose of this study is to determine if a treatment guideline using an adjunctive ketamine infusion improves outcomes in patients suffering from severe ethanol withdrawal. Retrospective observational cohort study. Academic tertiary care hospital. Patients admitted to the ICU and diagnosed with delirium tremens by Diagnostic and Statistical Manual of Mental Disorders V criteria. Pre and post guideline, all patients were treated in a symptom-triggered fashion with benzodiazepines and/or phenobarbital. Postguideline, standard symptom-triggered dosing continued as preguideline, plus, the patient was initiated on an IV ketamine infusion at 0.15-0.3 mg/kg/hr continuously until delirium resolved. Based upon withdrawal severity and degree of agitation, a ketamine bolus (0.3 mg/kg) was provided prior to continuous infusion in some patients. A total of 63 patients were included (29 preguideline; 34 postguideline). Patients treated with ketamine were less likely to be intubated (odds ratio, 0.14; p < 0.01; 95% CI, 0.04-0.49) and had a decreased ICU stay by 2.83 days (95% CI, -5.58 to -0.089; p = 0.043). For ICU days outcome, correlation coefficients were significant for alcohol level and total benzodiazepine dosing. For hospital days outcome, correlation coefficients were significant for patient age, aspartate aminotransferase, and alanine aminotransferase level. Regression revealed the use of ketamine was associated with a nonsignificant decrease in hospital stay by 3.66 days (95% CI, -8.40 to 1.08; p = 0.13). Mechanistically, adjunctive therapy with ketamine may attenuate the demonstrated neuroexcitatory contribution of N-methyl-D-aspartate receptor stimulation in severe ethanol withdrawal, reduce the need for excessive gamma-aminobutyric acid agonist mediated-sedation, and limit associated morbidity. A ketamine infusion in patients with delirium tremens was

  16. Distinct effects of protracted withdrawal on affect, craving, selective attention and executive functions among alcohol-dependent patients.

    PubMed

    Cordovil De Sousa Uva, Mariana; Luminet, Olivier; Cortesi, Marie; Constant, Eric; Derely, Marc; De Timary, Philippe

    2010-01-01

    The present study examined the effects of protracted alcohol withdrawal on affectivity, craving, selective attention and executive functions (EFs) in alcohol-dependent patients. Selective attention (The D2 Cancellation Test), flexibility (Trail Making Test), inhibition (Stroop Task), decision making (Iowa Gambling Task), craving (Obsessive-Compulsive Drinking Scale) and state affectivity (Positive and Negative Affectivity Schedule) were assessed in alcohol-dependent patients (DSM-IV, n = 35) matched to non-alcohol-dependent participants (n = 22) at the onset (T1: day 1 or 2) and at the end (T2: days 14-18) of protracted withdrawal during rehab. Alcohol-dependent patients' abilities to focus their attention on relevant information, to switch from one pattern to another, to inhibit irrelevant information and to make advantageous choices were lower than those of control participants during both times of a withdrawal cure. No effect of time emerged from analyses for selective attention and EF deficits. Conversely, significant differences between T1 and T2 were observed for craving and affect scores indicating a weakening of alcohol craving and negative affect as well as an improvement of positive affect among patients from onset to the end of cure. Control functions of the Supervisory Attentional System (Norman and Shallice, 1986) were impaired and did not improve during a 3-week withdrawal cure, whereas alcohol craving and negative state affectivity significantly improved in parallel during this period. Implications for understanding the clinical processes of withdrawal are discussed.

  17. Heart rate variability and sympathetic skin response in male patients suffering from acute alcohol withdrawal syndrome.

    PubMed

    Bär, Karl-Jürgen; Boettger, Michael Karl; Neubauer, Rene; Grotelüschen, Marei; Jochum, Thomas; Baier, Vico; Sauer, Heinrich; Voss, Andreas

    2006-09-01

    Many symptoms of alcohol withdrawal (AW) such as tachycardia or elevated blood pressure might be explained by increased peripheral and central adrenergic activity. In contrast to many neurochemical studies of sympathetic activation during AW, only very few studies investigated autonomic balance using neurophysiological methods. We investigated heart rate variability (HRV) and sympathetic skin response (SSR) in male patients suffering from mild AW syndrome (n = 20, no treatment required) and in patients with moderate to severe AW syndrome (n = 20, clomethiazole treatment) in the acute stage. Sympathovagal influence was quantified using measures of time and frequency domain of HRV as well as modern nonlinear parameters (compression entropy). Furthermore, we obtained latencies and amplitudes of SSR to quantify isolated sympathetic influence. Measures were obtained during the climax of withdrawal symptomatology before treatment, 1 day after climax, and shortly before discharge from hospital. Alcohol withdrawal scores were obtained and correlated to autonomic measures. Ambulatory blood pressure and AW scores revealed characteristic withdrawal symptoms in both patient groups. Apart from the nonlinear parameter compression entropy, Hc, measures of HRV revealed no sign of autonomic dysfunction in contrast to the significantly increased heart rates at the time of admission. Latencies and amplitudes of SSR did not indicate any increase of sympathetic activity. A negative correlation was found between Hc and mental withdrawal symptoms. We show here that classical measures for autonomic nervous system activity such as HRV and SSR are not suitable for describing the autonomic changes seen in acute AW, although a major role for the sympathetic nervous system has been proposed. This might be due to multiple dysregulation of metabolites in AWS or to subtle alcohol-induced damage to neuronal structures, issues that should be addressed in future studies.

  18. Effects of repeated withdrawal from alcohol on recovery of cognitive impairment under abstinence and rate of relapse.

    PubMed

    Loeber, Sabine; Duka, Theodora; Welzel Márquez, Helga; Nakovics, Helmut; Heinz, Andreas; Mann, Karl; Flor, Herta

    2010-01-01

    Several authors suggest that withdrawal from alcohol could cause neurotoxic lesions in the frontal lobe and thereby affect cognitive function. In line with this, previous studies have demonstrated greater cognitive impairment of alcohol-dependent patients with two or more previous detoxifications (Hi-detox) compared with patients with less than two detoxifications (Lo-detox). The aim of the present study was to investigate whether repeated withdrawal from alcohol affects recovery of cognitive function and is related to relapse. Forty-eight alcohol-dependent patients (Hi-detox: n = 31, Lo-detox: n = 17) and 36 healthy controls underwent a comprehensive neuropsychological test-battery. Patients were tested after completion of detoxification (T1) and 3 (T2, n = 35) and 6 (T3, n = 28) months after discharge. Healthy controls were tested at T1 (n = 36) and T2 (n = 16). Drinking behaviour was assessed at all times. Patients performed significantly worse than controls at T1 as well as T2 with regard to attention/executive function. Recovery of attention/executive function was observed within the second 3 months after discharge, but the Hi-detox group performed worse than the Lo-detox group. No association with relapse was observed. This study provides first evidence, that repeated withdrawal from alcohol might be associated with reduced brain plasticity as indicated by a delay of recovery from impairment of attention/executive function. However, little evidence was found for a direct influence of cognitive impairment on treatment success.

  19. Development of an alcohol withdrawal protocol: CNS collaborative exemplar.

    PubMed

    Phillips, Susan; Haycock, Camille; Boyle, Deborah

    2006-01-01

    The purpose of this process improvement project was to develop an Alcohol Withdrawal Syndrome (AWS) management protocol for acute care. The prevalence of alcohol abuse in our society presents challenges for health professionals, and few nurses have received formal education on the identification and treatment of AWS, which has frequently resulted in ineffective, nonstandardized care. However, nurses practicing in medical-surgical, emergency, trauma, and critical care settings must be astute in the assessment and management of AWS. DESIGN/BACKGROUND/RATIONALE: Following an analysis of existing management protocols, a behavioral health clinical nurse specialist was asked to lead a work team composed of physicians, pharmacists, and nurses to develop a new evidence-based alcohol withdrawal protocol for acute care. By implementing a standardized assessment tool and treatment protocol, clinical nurse specialists empowered nursing staff with strategies to prevent the serious medical complications associated with AWS. FINDINGS/OUTCOMES: The development and integration of a safe and effective treatment protocol to manage AWS was facilitated by collaborative, evidence-based decision making. Clinical experience and specialty expertise were integrated by clinical nurse specialists skilled in group dynamics, problem-solving, and the implementation of change. Improving care of patients in AWS is an exemplar for clinical nurse specialist roles as change agent and patient advocate.

  20. A systematic nurse-led approach to withdrawal risk screening, prevention and treatment among inpatients with an alcohol use disorder in an ear, nose, throat and jaw surgery department-A formative evaluation.

    PubMed

    Leuenberger, Deborah Linda; Fierz, Katharina; Hinck, Andreas; Bodmer, Daniel; Hasemann, Wolfgang

    2017-02-01

    Among patients with head and neck cancer comorbid alcohol use disorder is frequent which contributes to higher risk of developing perioperative alcohol withdrawal syndrome/delirium or delirium due to medical conditions. Although guidelines emphasize prevention and treatment of alcohol withdrawal in hospitalized patients, a validated systematic approach for management of these patients is still lacking. Our aim was to formatively evaluate our newly developed systematic approach in view of nurses' adherence to screening patients for regular alcohol consumption and managing their withdrawal symptoms using the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised. We conducted a formative evaluation to improve the project's design and performance and used a retrospective chart review in a consecutive sample of all adult inpatients with head and neck cancer being assigned for surgery in a university hospital. Our bundle of interventions consisted of nurses' screenings for regular alcohol consumption, withdrawal risk assessment, offering patients a substitution therapy, nurses' assessments of withdrawal symptoms and symptom oriented withdrawal management. Proximate endpoints were analyzed descriptively at each component of the bundle in terms of frequencies and severity of withdrawal symptoms, frequencies of nurses' and doctors' screenings and nurses' assessments performed as required. Between 2013 and 2014, 87 inpatients met inclusion criteria and screenings by doctors/ nurses revealed 49 alcohol consumers, where six screenings were omitted by nurses and six by doctors. Twenty-one consumers were at risk and six of them developed an alcohol withdrawal syndrome. None of the 87 showed an alcohol withdrawal delirium, but five developed a delirium due to medical conditions. Nurses correctly conducted all preventive elements of the intervention bundle in 14 (58%) patients at risk but overall, only performed 50% of the required assessments. Although nurses safely

  1. Involvement of delta opioid receptors in alcohol withdrawal-induced mechanical allodynia in male C57BL/6 mice.

    PubMed

    Alongkronrusmee, Doungkamol; Chiang, Terrance; van Rijn, Richard M

    2016-10-01

    As a legal drug, alcohol is commonly abused and it is estimated that 17 million adults in the United States suffer from alcohol use disorder. Heavy alcoholics can experience withdrawal symptoms including anxiety and mechanical allodynia that can facilitate relapse. The molecular mechanisms underlying this phenomenon are not well understood, which stifles development of new therapeutics. Here we investigate whether delta opioid receptors (DORs) play an active role in alcohol withdrawal-induced mechanical allodynia (AWiMA) and if DOR agonists may provide analgesic relief from AWiMA. To study AWiMA, adult male wild-type and DOR knockout C57BL/6 mice were exposed to alcohol by a voluntary drinking model or oral gavage exposure model, which we developed and validated here. We also used the DOR-selective agonist TAN-67 and antagonist naltrindole to examine the involvement of DORs in AWiMA, which was measured using a von Frey model of mechanical allodynia. We created a robust model of alcohol withdrawal-induced anxiety and mechanical allodynia by orally gavaging mice with 3g/kg alcohol for three weeks. AWiMA was exacerbated and prolonged in DOR knockout mice as well as by pharmacological blockade of DORs compared to control mice. However, analgesia induced by TAN-67 was attenuated during withdrawal in alcohol-gavaged mice. DORs appear to play a protective role in the establishment of AWiMA. Our current results indicate that DORs could be targeted to prevent or reduce the development of AWiMA during alcohol use; however, DORs may be a less suitable target to treat AWiMA during active withdrawal. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Cardiovascular Events in Alcoholic Syndrome With Alcohol Withdrawal History: Results From the National Inpatient Sample.

    PubMed

    Krishnamoorthy, Parasuram; Kalla, Aditi; Figueredo, Vincent M

    2018-05-01

    Epidemiologic studies suggest reduced cardiovascular disease (CVD) events with moderate alcohol consumption. However, heavy and binge drinking may be associated with higher CVD risk. Utilizing the Nationwide Inpatient Sample, we studied the association between a troublesome alcohol history (TAH), defined as those with diagnoses of both chronic alcohol syndrome and acute withdrawal history and CVD events. Patients >18 years with diagnoses of both chronic alcohol syndrome and acute withdrawal using the International Classification of Diseases-Ninth Edition-Clinical Modification (ICD-9-CM) codes 303.9 and 291.81, were identified in the Nationwide Inpatient Sample 2009-2010 database. Demographics, including age and sex, as well as CVD event rates were collected. Patients with TAH were more likely to be male, with a smoking history and have hypertension, with less diabetes, hyperlipidemia and obesity. After multimodal adjusted regression analysis, odds of coronary artery disease, acute coronary syndrome, in-hospital death and heart failure were significantly lower in patients with TAH when compared to the general discharge patient population. Utilizing a large inpatient database, patients with TAH had a significantly lower prevalence of CVD events, even after adjusting for demographic and traditional risk factors, despite higher tobacco use and male sex predominance, when compared to the general patient population. Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  3. Prolonged, severe intrathecal baclofen withdrawal syndrome: a case report.

    PubMed

    Hansen, Colby R; Gooch, Judith L; Such-Neibar, Teresa

    2007-11-01

    Intrathecal baclofen (ITB) withdrawal is a well-recognized complication when drug delivery is disrupted for any reason. ITB withdrawal varies widely in its severity and poses the very real possibility of death if not promptly managed. Cases of withdrawal lasting greater than 1 or 2 weeks, however, are sparse. We report the case of an 11-year-old girl with spastic quadriplegic cerebral palsy who developed an infected pump and subsequent meningitis, prompting the removal of her pump and catheter. She subsequently developed a severe, prolonged baclofen withdrawal syndrome marked by increased spasticity, agitation, hypertension, and tachycardia that lasted nearly 2 months, requiring intensive care and continuous intravenous sedation with benzodiazepines and opiates. Her pump was eventually replaced on hospital day 56 and within 24 hours her symptoms dramatically improved. She was eventually weaned off sedating medications and returned to baseline functional status. Typical management of baclofen withdrawal is reviewed. To date, the literature has not discussed the potential role for opiates in managing baclofen withdrawal, yet a growing body of literature is examining the interplay between opiates and gamma-aminobutyric acid B pathways. A potential role for opiates in managing severe baclofen withdrawal is proposed.

  4. Diverse autonomic regulation of pupillary function and the cardiovascular system during alcohol withdrawal.

    PubMed

    Jochum, Thomas; Hoyme, Johannes; Schulz, Steffen; Weißenfels, Markus; Voss, Andreas; Bär, Karl-Jürgen

    2016-02-01

    Previous research indicated the complexity of autonomic dysfunction during acute alcohol withdrawal. This study aimed to investigate the pupillary light reflex as an indicator of midbrain and brainstem regulatory systems in relation to cardiovascular autonomic function. Thirty male patients were included in the study. They were investigated during acute alcohol withdrawal syndrome and 24h later during clomethiazole treatment and compared to healthy controls. Parameters of pupillary light reflex of both eyes as well as heart rate variability, blood pressure variability and baroreflex sensitivity (BRS) were studied. We observed significantly reduced sympathetic (small diameter, e.g., left eye: 5.00 in patients vs. 5.91 mm in controls) and vagal modulation (e.g., prolonged latencies, left eye: 0.28 vs. 0.26 ms) regarding both pupils during acute alcohol withdrawal syndrome. Cardiovascular parameters showed reduced vagal modulation (e.g., b-slope of BRS: 7. 57 vs. 13.59 ms/mm Hg) and mixed results for sympathetic influence. After 24h, autonomic dysfunction improved significantly, both for the pupils (e.g., left diameter: 5.38 mm) and the heart (e.g., b-slope of BRS: 9.34 ms/mm Hg). While parameters obtained from the pupil correlated with cardiac autonomic function (e.g, BRS and left diameter: r=0.564) in healthy controls, no such pattern was observed in patients. Results obtained from the pupil during acute alcohol withdrawal do not simply mirror autonomic dysfunction regarding the heart. Pupillary and cardiovascular changes after 24h indicate state dependencies of the results. The findings are discussed with respect to autonomic mechanisms and potentially involved brain regions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Motor impairment: a new ethanol withdrawal phenotype in mice

    PubMed Central

    Philibin, Scott D.; Cameron, Andy J.; Metten, Pamela; Crabbe, John C.

    2015-01-01

    Alcoholism is a complex disorder with genetic and environmental risk factors. The presence of withdrawal symptoms is one criterion for alcohol dependence. Genetic animal models have followed a reductionist approach by quantifying various effects of ethanol withdrawal separately. Different ethanol withdrawal symptoms may have distinct genetic etiologies, and therefore differentiating distinct neurobiological mechanisms related to separate signs of withdrawal would increase our understanding of various aspects of the complex phenotype. This study establishes motor incoordination as a new phenotype of alcohol withdrawal in mice. Mice were made physically dependent on ethanol by exposure to ethanol vapor for 72 h. The effects of ethanol withdrawal in mice from different genetic backgrounds were measured on the accelerating rotarod, a simple motor task. Ethanol withdrawal disrupted accelerating rotarod behavior in mice. The disruptive effects of withdrawal suggest a performance rather than a learning deficit. Inbred strain comparisons suggest genetic differences in magnitude of this withdrawal phenotype. The withdrawal-induced deficits were not correlated with the selection response difference in handling convulsion severity in selectively bred Withdrawal Seizure-Prone and Withdrawal Seizure-Resistant lines. The accelerating rotarod seems to be a simple behavioral measure of ethanol withdrawal that is suitable for comparing genotypes. PMID:18690115

  6. Phenobarbital compared to benzodiazepines in alcohol withdrawal treatment: A register-based cohort study of subsequent benzodiazepine use, alcohol recidivism and mortality.

    PubMed

    Askgaard, Gro; Hallas, Jesper; Fink-Jensen, Anders; Molander, Anna Camilla; Madsen, Kenneth Grønkjær; Pottegård, Anton

    2016-04-01

    Long-acting benzodiazepines such as chlordiazepoxide are recommended as first-line treatment for alcohol withdrawal. These drugs are known for their abuse liability and might increase alcohol consumption among problem drinkers. Phenobarbital could be an alternative treatment option, possibly with the drawback of a more pronounced acute toxicity. We evaluated if phenobarbital compared to chlordiazepoxide decreased the risk of subsequent use of benzodiazepines, alcohol recidivism and mortality. The study was a register-based cohort study of patients admitted for alcohol withdrawal 1998-2013 and treated with either phenobarbital or chlordiazepoxide. Patients were followed for one year. We calculated hazard ratios (HR) for benzodiazepine use, alcohol recidivism and mortality associated with alcohol withdrawal treatment, while adjusting for confounders. A total of 1063 patients treated with chlordiazepoxide and 1365 patients treated with phenobarbital were included. After one year, the outcome rates per 100 person-years in the phenobarbital versus the chlordiazepoxide cohort were 9.20 vs. 5.13 for use of benzodiazepine, 37.9 vs. 37.9 for alcohol recidivism and 29 vs. 59 for mortality. Comparing phenobarbital to chlordiazepoxide treated, the HR of subsequent use of benzodiazepines was 1.56 (95%CI 1.05-2.30). Similarly, the HR for alcohol recidivism was 0.99 (95%CI 0.84-1.16). Lastly, the HR for 30-days and 1 year mortality was 0.25 (95%CI 0.08-0.78) and 0.51 (95%CI 0.31-0.86). There was no decreased risk of subsequent benzodiazepine use or alcohol recidivism in patients treated with phenobarbital compared to chlordiazepoxide. Phenobarbital treatment was associated with decreased mortality, which might be confounded by somatic comorbidity among patients receiving chlordiazepoxide. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Dexmedetomidine infusion as adjunctive therapy to benzodiazepines for acute alcohol withdrawal.

    PubMed

    Darrouj, Jamil; Puri, Nitin; Prince, Erin; Lomonaco, Anthony; Spevetz, Antoinette; Gerber, David R

    2008-11-01

    To report a case of alcohol withdrawal and delirium tremens successfully treated with adjunctive dexmedetomidine. A 30-year-old man with a history of alcohol abuse was admitted to the general medical unit because of altered mental status and agitation. He was initially treated for alcohol withdrawal with benzodiazepines; his condition then deteriorated and he was transferred to the intensive care unit. Because of the patient's poor response to benzodiazepines (oxazepam and lorazepam, with midazolam the last one used), intravenous dexmedetomidine was started at an initial dose of 0.2 microg/kg/h and titrated to 0.7 microg/kg/h to the patient's comfort. Midazolam was subsequently tapered to discontinuation due to excessive sedation. In the intensive care unit, the patient's symptoms remained controlled with use of dexmedetomidine alone. He remained in the intensive care unit for 40 hours; dexmedetomidine was then tapered to discontinuation and the patient was transferred back to the general medical unit on oral oxazepam and thiamine, which had been started in the emergency department. He was discharged after 5 days. A review of the PubMed database (1989-2007) failed to identify any other instances of dexmedetomidine having been used as the principal agent to treat alcohol withdrawal. The use of sedative to treat delirium tremens is well documented, with benzodiazepines being the agents of choice. The clinical utility of benzodiazepines is limited by their stimulation of the gamma-aminobutyric acid receptors, an effect not shared by dexmedetomidine, a central alpha(2)-receptor agonist that induces a state of cooperative sedation and does not suppress respiratory drive. In patients with delirium tremens, dexmedetomidine should be considered as an option for primary treatment. This case illustrates the need for further studies to investigate other potential uses for dexmedetomidine.

  8. Psychosocial withdrawal characteristics of nicotine compared with alcohol and caffeine.

    PubMed

    Miyata, Hisatsugu; Hironaka, Naoyuki; Takada, Kohji; Miyasato, Katsumasa; Nakamura, Koichi; Yanagita, Tomoji

    2008-10-01

    The purpose of the present study was to observe the psychosocial characteristics of withdrawal from cigarette smoking in comparison with those from caffeine (CAF) and alcoholic (ALC) beverage withdrawal. Twenty-seven healthy volunteers at a medial level of dependence on both cigarettes (nicotine, NCT) and either CAF or ALC, as judged by the DSM-IV-TR criteria for substance dependence, participated in this study. The participants were required to abstain from smoking and either CAF or ALC for 7 days, each one after another, with a 7-day interval. The order of abstinence was counterbalanced among the participants. Psychosocial parameters, including a desire for substances, social activity function, well-being, withdrawal symptoms, and vital signs, were assessed during the withdrawal periods. The study protocol was approved by the Jikei University Review Board. The results indicated that there were no differences in the maximum level of desire for a substance and the influence on social activity function between NCT and other substances during the withdrawal periods. As for withdrawal symptoms, NCT caused a more intensive degree of irritability than CAF or ALC, and a more intensive degree of difficulty concentrating and restlessness than did withdrawal from ALC. However, the subjective well-being questionnaire indicated no differences in these symptoms between NCT and other substances. The present results suggest that there are no significant differences in psychosocial manifestations regarding the difficulty in abstaining from NCT, CAF, and ALC.

  9. Effects of chronic alcohol consumption, withdrawal and nerve growth factor on neuropeptide Y expression and cholinergic innervation of the rat dentate hilus.

    PubMed

    Pereira, Pedro A; Rocha, João P; Cardoso, Armando; Vilela, Manuel; Sousa, Sérgio; Madeira, M Dulce

    2016-05-01

    Several studies have demonstrated the vulnerability of the hippocampal formation (HF) to chronic alcohol consumption and withdrawal. Among the brain systems that appear to be particularly vulnerable to the effects of these conditions are the neuropeptide Y (NPY)-ergic and the cholinergic systems. Because these two systems seem to closely interact in the HF, we sought to study the effects of chronic alcohol consumption (6months) and subsequent withdrawal (2months) on the expression of NPY and on the cholinergic innervation of the rat dentate hilus. As such, we have estimated the areal density and the somatic volume of NPY-immunoreactive neurons, and the density of the cholinergic varicosities. In addition, because alcohol consumption and withdrawal are associated with impaired nerve growth factor (NGF) trophic support and the administration of exogenous NGF alters the effects of those conditions on various cholinergic markers, we have also estimated the same morphological parameters in withdrawn rats infused intracerebroventricularly with NGF. NPY expression increased after withdrawal and returned to control values after NGF treatment. Conversely, the somatic volume of these neurons did not differ among all groups. On other hand, the expression of vesicular acetylcholine transporter (VAChT) was reduced by 24% in ethanol-treated rats and by 46% in withdrawn rats. The administration of NGF to withdrawn rats increased the VAChT expression to values above control levels. These results show that the effects of prolonged alcohol intake and protracted withdrawal on the hilar NPY expression differ from those induced by shorter exposures to ethanol and by abrupt withdrawal. They also suggest that the normalizing effect of NGF on NPY expression might rely on the NGF-induced improvement of cholinergic neurotransmission in the dentate hilus. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Symptom-Triggered vs. Fixed-Dosing Management of Alcohol Withdrawal Syndrome.

    PubMed

    Skinner, Reagan T

    2014-01-01

    A literature review was conducted with the objective of creating evidence-based recommendations for use of symptom-triggered therapy (STT) or fixed-schedule dosing in treating alcohol withdrawal syndrome in inpatients. Use of STT reduced duration of therapy as well as the number of patients requiring treatment or medication, potentially reducing costs and risk of adverse medication reactions.

  11. Physical dependence on nitrous oxide in mice: resemblance to alcohol but not to opiate withdrawal.

    PubMed

    Milne, B; Cervenko, F W; Jhamandas, K H

    1981-01-01

    Mice of two strains, Crl:CD-1(1CR)Br and C57BL6, were exposed to nitrous oxide at concentrations of 50, 65 and 80 per cent for 34 or 68 hours. Cessation of nitrous oxide resulted in characteristic convulsions similar to those seen in alcohol withdrawal in all mice. These peaked in severity within 2-3 minutes after removal from nitrous oxide and declined over 6 hours. The severity and duration of these convulsions were related to the nitrous oxide concentration and duration of exposure. Naloxone or naltrexone produced no significant increase in severity of convulsions. The narcotic antagonists did not precipitate acute weight loss or characteristic jumping behaviour seen in animals dependent on opiates. These results demonstrate that chronic exposure to nitrous oxide results in development of physical dependence which resembles alcohol and not opiate dependence. Analgesia and physical dependence produced by nitrous oxide appear to be mediated through separate mechanisms.

  12. Assessment and management of alcohol dependence and withdrawal in the acute hospital: concise guidance.

    PubMed

    Stewart, Stephen; Swain, Sharon

    2012-06-01

    Alcohol dependence is common among patients attending acute hospitals. It can be the major reason for attendance or a significant cofactor. Assessment of these patients in the acute setting can be challenging owing to the multidisciplinary approach required. Doctors in acute hospitals are often inexperienced in managing dependence, a mental health problem. They might focus on the physical harms or the withdrawal, a consequence of the dependence. For this reason, assessment of dependence and prevention and management of acute alcohol withdrawal are often suboptimal. There is little existing guidance on how to manage this patient population, especially in non-specialist settings. With recently published National Institute for Health and Clinical Excellence (NICE) guidance on the management of dependence and withdrawal, now is the perfect time to produce concise guidelines in the hope that a more succinct suite of guidance can reach a larger audience.

  13. The craving withdrawal model for alcoholism: towards the DSM-V. Improving the discriminant validity of alcohol use disorder diagnosis.

    PubMed

    de Bruijn, Carla; van den Brink, Wim; de Graaf, Ron; Vollebergh, Wilma A M

    2005-01-01

    To compare the discriminant validity of the DSM-IV and the ICD-10 classification of alcohol use disorders (AUD) with an alternative classification, the craving withdrawal model (CWM). CWM requires craving and withdrawal for the diagnosis of alcohol dependence and raises the alcohol abuse threshold to two DSM-IV AUD criteria. Data were derived from The Netherlands Mental Health Survey and Incidence Study, a large representative sample of the general Dutch population. In the present study, only non-abstinent subjects were included (n=6041). Three diagnostic systems (DSM-IV, ICD-10, and CWM) were compared using the following discriminant variables: alcohol intake, psychiatric comorbidity, functional status, familial alcohol problems, and treatment sought. The year prevalence of CWM alcohol dependence was lower than the prevalence of ICD-10 and DSM-IV dependence (0.3% vs 1.4% and 1.4%). The year prevalence of abuse was similar for CWM and DSM-IV (4.7 and 4.9%), but lower for ICD-10 harmful use (1.7%). DSM-IV resulted in a poor distinction between normality and abuse and ICD-10 resulted in a poor distinction between harmful use and dependence. In contrast, the CWM distinctions between normality and abuse, and between abuse, and dependence were significant for most of the discriminant variables. This study indicates that CWM improves the discriminant validity of AUD diagnoses. The predictive validity of the CWM for alcohol and other substance use disorders remain to be studied.

  14. Rescuing prefrontal cAMP-CREB pathway reverses working memory deficits during withdrawal from prolonged alcohol exposure.

    PubMed

    Dominguez, G; Dagnas, M; Decorte, L; Vandesquille, M; Belzung, C; Béracochéa, D; Mons, N

    2016-03-01

    Both human and animal studies indicate that alcohol withdrawal following chronic alcohol consumption (CAC) impairs many of the cognitive functions which rely on the prefrontal cortex (PFC). A candidate signaling cascade contributing to memory deficits during alcohol withdrawal is the protein kinase A (PKA)/cAMP-responsive element binding (CREB) cascade, although the role of PKA/CREB cascade in behavioral and molecular changes during sustained withdrawal period remains largely unknown. We demonstrated that 1 week (1W) or 6 weeks (6W) withdrawal after 6-month CAC impairs working memory (WM) in a T-maze spontaneous alternation task and reduces phosphorylated CREB (pCREB) in the PFC but not the dorsal CA1 region (dCA1) of the hippocampus compared with CAC and water conditions. In contrast, both CAC-unimpaired and withdrawn-impaired mice exhibited decreased pCREB in dCA1 as well as reduced histone H4 acetylation in PFC and dCA1, compared with water controls. Next, we showed that enhancing CREB activity through rolipram administration prior to testing improved WM performance in withdrawn mice but impaired WM function in water mice. In addition, WM improvement correlates positively with increased pCREB level selectively in the PFC of withdrawn mice. Results further indicate that direct infusion of the PKA activator (Sp-cAMPS) into the PFC significantly improves or impairs, respectively, WM performance in withdrawn and water animals. In contrast, Sp-cAMPS had no effect on WM when infused into the dCA1. Collectively, these results provide strong support that dysregulation of PKA/CREB-dependent processes in prefrontal neurons is a critical molecular signature underlying cognitive decline during alcohol withdrawal.

  15. Attenuation of Ethanol Withdrawal by Ceftriaxone-Induced Upregulation of Glutamate Transporter EAAT2

    PubMed Central

    Abulseoud, Osama A; Camsari, Ulas M; Ruby, Christina L; Kasasbeh, Aimen; Choi, Sun; Choi, Doo-Sup

    2014-01-01

    Alcohol withdrawal syndrome (AWS) is a potentially fatal outcome of severe alcohol dependence that presents a significant challenge to treatment. Although AWS is thought to be driven by a hyperglutamatergic brain state, benzodiazepines, which target the GABAergic system, comprise the first line of treatment for AWS. Using a rat model of ethanol withdrawal, we tested whether ceftriaxone, a β-lactam antibiotic known to increase the expression and activity of glutamate uptake transporter EAAT2, reduces the occurrence or severity of ethanol withdrawal manifestations. After a 2-week period of habituation to ethanol in two-bottle choice, alcohol-preferring (P) and Wistar rats received ethanol (4.0 g/kg) every 6 h for 3–5 consecutive days via gavage. Rats were then deprived of ethanol for 48 h during which time they received ceftriaxone (50 or 100 mg/kg, IP) or saline twice a day starting 12 h after the last ethanol administration. Withdrawal manifestations were captured by continuous video recording and coded. The evolution of ethanol withdrawal was markedly different for P rats vs Wistar rats, with withdrawal manifestations occurring >12 h later in P rats than in Wistar rats. Ceftriaxone 100 mg/kg per injection twice per day (200 mg/kg/day) reduced or abolished all manifestations of ethanol withdrawal in both rat variants and prevented withdrawal-induced escalation of alcohol intake. Finally, ceftriaxone treatment was associated with lasting upregulation of ethanol withdrawal-induced downregulation of EAAT2 in the striatum. Our data support the role of ceftriaxone in alleviating alcohol withdrawal and open a novel pharmacologic avenue that requires clinical evaluation in patients with AWS. PMID:24452391

  16. Delirium tremens and alcohol withdrawal nationally in the Veterans Health Administration.

    PubMed

    Moore, David Thomas; Fuehrlein, Brian Scott; Rosenheck, Robert Alan

    2017-10-01

    Alcohol withdrawal-especially delirium tremens (DT)-is a potentially life-threatening condition. While short-term treatment regimens and factors that predispose to more severe symptomatology have been extensively studied, little attention has been paid to the clinical epidemiology and long-term care of the chronic medical, addictive, psychiatric, and psychosocial problems faced by these patients. National Veterans Health Administration data from fiscal year 2012 were examined to identify veterans diagnosed with DT; with withdrawal but not DT (WNDT); and with Alcohol Use Disorder (AUD) but neither DT nor WNDT. They were compared on sociodemographic characteristics, psychiatric and medical co-morbidities, and health service and psychotropic medication use, first with bivariate analyses and then multiple logistic regression. Among the 345,297 veterans diagnosed with AUD, 2,341 (0.7%) were diagnosed with DT and 6,738 (2.0%) with WNDT. Veterans diagnosed with either WNDT or DT were more likely to have been homeless, had more comorbid medical and psychiatric disorders, were more likely to be diagnosed with drug use disorders, utilized more health services, received more psychotropic medications, and were more likely to receive naltrexone. They were more likely to receive specialized legal, housing, vocational, and psychosocial rehabilitation services, as well as intensive case management. Adults with WNDT and DT suffer from multiple chronic conditions and long-term service models are needed to coordinate the work of multiple specialists and to assure continuity of care. This national study identifies sociodemographic characteristics, comorbidities, and service utilization patterns associated with WNDT and DT.(Am J Addict 2017;26:722-730). © 2017 American Academy of Addiction Psychiatry.

  17. Time-dependent negative reinforcement of ethanol intake by alleviation of acute withdrawal

    PubMed Central

    Cunningham, Christopher L.; Fidler, Tara L.; Murphy, Kevin V.; Mulgrew, Jennifer A.; Smitasin, Phoebe J.

    2012-01-01

    Background Drinking to alleviate the symptoms of acute withdrawal is included in diagnostic criteria for alcoholism, but the contribution of acute withdrawal relief to high alcohol intake has been difficult to model in animals. Methods Ethanol dependence was induced by passive intragastric ethanol infusions in C57BL/6J (B6) and DBA/2J (D2) mice; non-dependent controls received water infusions. Mice were then allowed to self-administer ethanol or water intragastrically. Results The time course of acute withdrawal was similar to that produced by chronic ethanol vapor exposure in mice, reaching a peak at 7-9 h and returning to baseline within 24 h; withdrawal severity was greater in D2 than in B6 mice (Exp. 1). Post-withdrawal delays in initial ethanol access (1, 3 or 5 days) reduced the enhancement in later ethanol intake normally seen in D2 (but not B6) mice allowed to self-infuse ethanol during acute withdrawal (Exp. 2). The post-withdrawal enhancement of ethanol intake persisted over a 5-d abstinence period in D2 mice (Exp. 3). D2 mice allowed to drink ethanol during acute withdrawal drank more ethanol and self-infused more ethanol than non-dependent mice (Exp. 4). Conclusions Alcohol access during acute withdrawal increased later alcohol intake in a time-dependent manner, an effect that may be related to a genetic difference in sensitivity to acute withdrawal. This promising model of negative reinforcement encourages additional research on the mechanisms underlying acute withdrawal relief and its role in determining risk for alcoholism. PMID:22999529

  18. Comparison of cannabis and tobacco withdrawal: severity and contribution to relapse.

    PubMed

    Budney, Alan J; Vandrey, Ryan G; Hughes, John R; Thostenson, Jeff D; Bursac, Zoran

    2008-12-01

    This naturalistic telephone survey study compared perceptions of withdrawal severity in 67 daily cannabis users and 54 daily tobacco cigarette smokers who made quit attempts during the prior 30 days. A Withdrawal Symptom Checklist assessed the severity of abstinence symptoms and a Likert scale assessed perceived relations between abstinence symptoms and relapse. A composite Withdrawal Discomfort Score did not differ significantly between groups (M = 13.0 for cannabis, vs. M = 13.2 for tobacco). Individual symptom severity ratings were also of similar magnitude, except craving and sweating were slightly higher for tobacco. Both groups reported that withdrawal contributed substantially to relapse, and the strength of these ratings was similar across groups. The diverse convenience sample examined in this study adds external validity and generalizability to prior studies that included only users not planning to quit or excluded many common types of cannabis users. The comparable withdrawal experience from these heterogeneous cannabis and tobacco users supports previous findings from controlled laboratory studies and indicates that real-world, frequent cannabis users perceive that withdrawal symptoms negatively affect their desire and ability to quit.

  19. Gamma-hydroxybutyrate (GHB) for treatment of alcohol withdrawal and prevention of relapses.

    PubMed

    Leone, Maurizio A; Vigna-Taglianti, Federica; Avanzi, Giancarlo; Brambilla, Romeo; Faggiano, Fabrizio

    2010-02-17

    Chronic excessive alcohol consumption may lead to dependence, and to alcohol withdrawal syndrome (AWS) in case of abrupt drinking cessation. Gamma-hydroxybutyric acid (GHB) can prevent and suppress withdrawal symptoms, and improve the medium-term abstinence rate. A clear balance between effectiveness and harmfulness has not been yet established. To evaluate the efficacy and safety of GHB for treatment of AWS and prevention of relapse We searched Cochrane Drugs and Alcohol Group' Register of Trials (October 2008), PubMed, EMBASE, CINAHL (January 2005 - October 2008), EconLIT (1969 to February 2008), reference list of retrieved articles Randomized controlled trials (RCTs) and Controlled Prospective Studies (CPS) evaluating the efficacy and the safety of GHB vs placebo or other pharmacological treatments. Three authors independently extracted data and assessed the methodological quality of studies. Thirteen RCTs were included. Eleven studies were conducted in Italy.For withdrawal syndrome, comparing GHB 50mg with placebo, results from 1 study, 23 participants favour GHB for withdrawal symptoms: WMD -12.1 (95% CI, -15.9 to -8.29) and side effects were more frequent in the placebo group: RR 16.2 (95% CI, 1.04 to 254.9).In the comparison with Chlormetiazole, for GHB 50mg, results from 1 study, 21 participants favour GHB for withdrawal symptoms: MD -3.40 (95% CI -5.09 to -1.71), for GHB 100mg, results from 1 study, 98 participants favour anticonvulsants for side effects: RR 1.84 (95% CI 1.19 to 2.85).At mid-term, comparing GHB with placebo, results favour GHB for abstinence rate (RR 5.35; 1.28-22.4), controlled drinking (RR 2.13; 1.07-5.54), relapses (RR 0.36; 0.21-0.63), and number of daily drinks (WMD -4.60; -6.18 to -3.02). GHB performed better than NTX and Disulfiram on abstinence (RR 2.59; 1.35-4.98, RR 1.66; 0.99-2.80 respectively). The association of GHB and NTX was better than NTX on abstinence (RR 12.2; 1.79-83.9), as well was the association of NTX, GHB and

  20. Prazosin + naltrexone decreases alcohol drinking more effectively than does either drug alone in P rats with a protracted history of extensive voluntary alcohol drinking, dependence and multiple withdrawals

    PubMed Central

    Rasmussen, Dennis D; Kincaid, Carrie L; Froehlich, Janice C

    2015-01-01

    Background Prazosin (PRZ, an α1-adrenergic receptor antagonist) and naltrexone (NTX, a non-specific opioid receptor antagonist) each decrease alcohol drinking when administered to rats selectively-bred for high voluntary alcohol drinking (alcohol-preferring, or “P”), and the combination of PRZ+NTX decreases alcohol drinking more effectively than does either drug alone. Since drug responsiveness can depend on history of alcohol drinking and dependence, we investigated whether various schedules of PRZ and NTX administration, alone or in combination, are effective in decreasing alcohol drinking in male P rats with a history of protracted voluntary alcohol drinking, dependence and repeated withdrawals closely resembling human alcoholism. Methods Male P rats became alcohol-dependent during 1 year of ad libitum 24 h/day access to food, water and 20% alcohol with repetitive temporary alcohol withdrawals. Four sequential studies then addressed effects of oral PRZ (2 mg/kg) and NTX (10 mg/kg), alone or together, on alcohol drinking during: 1) daily alcohol access with daily drug treatment, 2) intermittent alcohol access with daily drug treatment, 3) intermittent alcohol access with occasional drug treatment, and 4) post-deprivation reinstatement of alcohol access. Results The combination of PRZ+NTX consistently suppressed alcohol drinking during daily or intermittent alcohol access conditions and when drug treatment was either daily or occasional. PRZ+NTX was consistently more effective than either drug alone. The reduction in alcohol drinking was not due to sedation, motor effects or malaise. Conclusions Both daily and “as-needed” treatment with PRZ+NTX are highly effective in suppressing daily, intermittent and post-deprivation alcohol drinking in male P rats with a protracted history of alcohol dependence and repeated withdrawals. This drug combination may be especially effective for treating individuals with long histories of heavy alcohol abuse, dependence and

  1. Low efficacy of non-opioid drugs in opioid withdrawal symptoms.

    PubMed

    Hermann, Derik; Klages, Eckard; Welzel, Helga; Mann, Karl; Croissant, Bernhard

    2005-06-01

    Opioid withdrawal, stress or cues associated with opioid consumption can induce opioid craving. If opioids are not available, opioid-dependent patients usually search for alternative drugs. Because several non-opioid drugs stimulate the endogenous opioidergic system, this concept may explain their frequent use by opioid-dependent patients. We hypothesized that non-opioid drugs alleviate opioid withdrawal symptoms and are therefore consumed by opioid addicts. We asked 89 opioid-dependent patients participating in an out-patient opioid maintenance program to estimate the potential of several non-opioid drugs in being able to alleviate opioid withdrawal. We applied a five-point Lickert scale (1 = very good reduction of opioid withdrawal; 5 = no reduction of opioid withdrawal). Patients could also indicate a worsening of opioid withdrawal. Values (mean +/- SD) were: for benzodiazepines, 3.2 +/- 1.1; tricyclic antidepressants, 3.6 +/- 1.1; cannabis, 3.6 +/- 1.0; alcohol, 4.1 +/- 1.1; cocaine, 4.2 +/- 1.1; amphetamine, 4.4 +/- 0.9; nicotine, 4.7 +/- 0.7; and caffeine, 4.9 +/- 0.5. A worsening of opioid withdrawal was reported by 62% of the patients for cocaine, 62% for amphetamine, 50% for caffeine, 37.5% for cannabis, 27% for nicotine, 26% for alcohol, 8% for tricyclic antidepressants and 3% for benzodiazepines. Our study shows a low efficacy of non-opioid drugs in alleviating opioid withdrawal symptoms. The data basis of this study was good and the sample was suitable to be asked for estimations of drug-drug interactions. Of the patients, 26 - 62% even reported a worsening of opioid withdrawal for cannabis, alcohol, cocaine and amphetamine. Only benzodiazepines and tricyclic antidepressants were reported to have a moderate positive effect on opioid withdrawal.

  2. Financial strain indirectly influences smoking cessation through withdrawal symptom severity.

    PubMed

    Kendzor, Darla E; Businelle, Michael S; Waters, Aaron F; Frank, Summer G; Hébert, Emily T

    2018-02-01

    Financial strain has an adverse impact on smoking cessation. However, the mechanisms through which financial strain influences cessation remain unclear. The purpose of the current study was to determine whether financial strain indirectly influenced smoking cessation through withdrawal symptom severity. Participants (N=139) were primarily Black (63.3%) and female (57.6%) adults enrolled in a smoking cessation program at a safety-net hospital. A self-report financial strain questionnaire was completed one week prior to the scheduled quit date, and the Wisconsin Smoking Withdrawal Scale (WSWS) was completed on the day after the scheduled quit date. Biochemically-verified 7-day point prevalence abstinence was assessed four weeks after the scheduled quit date. Adjusted mediation analyses were conducted using the PROCESS macro for SPSS to evaluate the indirect effects of financial strain on smoking cessation via post-quit withdrawal symptom severity. Analyses indicated a significant indirect effect of financial strain on smoking cessation through total withdrawal symptom severity, B=0.027; 95% CI (0.003, 0.066); and specifically anger, B=0.035; 95% CI (0.008, 0.074), anxiety, B=0.021; 95% CI (0.001, 0.051), and sleep symptoms, B=0.015; 95% CI (0.005, 0.043). Greater pre-quit financial strain was associated with greater post-quit withdrawal symptom severity, which increased the likelihood of non-abstinence 4 weeks after the scheduled quit attempt. The direct effect of financial strain on smoking cessation was not significant in any of the mediation models. Findings: suggest that withdrawal severity is an underlying mechanism through which financial strain influences smoking cessation. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Neurologic complications of alcoholism.

    PubMed

    Noble, James M; Weimer, Louis H

    2014-06-01

    This review serves as an overview of neurologic conditions associated with alcohol abuse or withdrawal, including epidemiology, clinical symptoms, diagnostic approach, and treatment. Frequent alcohol abuse and frank alcoholism are very common among adults in the United States. Although rates decline with each decade, as many as 10% of the elderly drink excessively. Given the ubiquitous nature of alcoholism in society, its complications have been clinically recognized for generations, with recent advances focusing on improved understanding of ethanol's biochemical targets and the pathophysiology of its complications. The chronic effects of alcohol abuse are myriad and include neurologic complications through both direct and indirect effects on the central and peripheral nervous systems. These disorders include several encephalopathic states related to alcohol intoxication, withdrawal, and related nutritional deficiencies; acute and chronic toxic and nutritional peripheral neuropathies; and myopathy. Although prevention of alcoholism and its neurologic complications is the optimal strategy, this article reviews the specific treatment algorithms for alcohol withdrawal and its related nutritional deficiency states.

  4. Alcohol Withdrawal-Induced Seizure Susceptibility is Associated with an Upregulation of CaV1.3 Channels in the Rat Inferior Colliculus

    PubMed Central

    Akinfiresoye, Luli R.; Allard, Joanne S.; Lovinger, David M.

    2015-01-01

    Background: We previously reported increased current density through L-type voltage-gated Ca2+ (CaV1) channels in inferior colliculus (IC) neurons during alcohol withdrawal. However, the molecular correlate of this increased CaV1 current is currently unknown. Methods: Rats received three daily doses of ethanol every 8 hours for 4 consecutive days; control rats received vehicle. The IC was dissected at various time intervals following alcohol withdrawal, and the mRNA and protein levels of the CaV1.3 and CaV1.2 α1 subunits were measured. In separate experiments, rats were tested for their susceptibility to alcohol withdrawal–induced seizures (AWS) 3, 24, and 48 hours after alcohol withdrawal. Results: In the alcohol-treated group, AWS were observed 24 hours after withdrawal; no seizures were observed at 3 or 48 hours. No seizures were observed at any time in the control-treated rats. Compared to control-treated rats, the mRNA level of the CaV1.3 α1 subunit was increased 1.4-fold, 1.9-fold, and 1.3-fold at 3, 24, and 48 hours, respectively. In contrast, the mRNA level of the CaV1.2 α1 subunit increased 1.5-fold and 1.4-fold at 24 and 48 hours, respectively. At 24 hours, Western blot analyses revealed that the levels of the CaV1.3 and CaV1.2 α1 subunits increased by 52% and 32%, respectively, 24 hours after alcohol withdrawal. In contrast, the CaV1.2 and CaV1.3 α1 subunits were not altered at either 3 or 48 hours during alcohol withdrawal. Conclusions: Expression of the CaV1.3 α1 subunit increased in parallel with AWS development, suggesting that altered L-type CaV1.3 channel expression is an important feature of AWS pathogenesis. PMID:25556199

  5. Comparative Evaluation of Partial α2 -Adrenoceptor Agonist and Pure α2 -Adrenoceptor Antagonist on the Behavioural Symptoms of Withdrawal after Chronic Alcohol Administration in Mice.

    PubMed

    Arora, Shivani; Vohora, Divya

    2016-08-01

    As an addictive drug, alcohol produces withdrawal symptoms if discontinued abruptly after chronic use. Clonidine (CLN), a partial α2 -adrenergic agonist, and mirtazapine (MRT), an antagonist of α2 -adrenoceptor, both clinically aid alcohol withdrawal. Considering different mechanisms of action of the two drugs, this study was designed to see how far these two mechanistically different drugs differ in their ability to decrease the severity of ethanol withdrawal syndrome. The effect of CLN and MRT on ethanol withdrawal-induced anxiety, depression and memory impairment was analysed using EPM, FST and PAR tests, respectively. Animals received distilled water, ethanol and/or either of the drugs (CLN and MRT) in different doses. Relapse to alcohol use was analysed by CPP test. Animals received ethanol as a conditioning drug and distilled water, CLN or MRT as test drug. CLN and MRT both alleviated anxiety in a dose-dependent manner. MRT (4 mg/kg) was more effective than CLN (0.1 mg/kg) in ameliorating the anxiogenic effect of alcohol withdrawal. However, CLN treatment increased depression. It significantly decreased swimming time and increased immobility time, whereas MRT treatment decreased immobility time and increased climbing and swimming time during abstinence. The effect was dose dependent for both drugs. The results of PAR test show that CLN treatment worsens working memory. Significant increase in SDE and TSZ and decrease in SDL were observed in CLN-treated animals. MRT treatment, on the other hand, improved working memory at both doses. Further, both CLN and MRT alleviated craving. A significant decrease in time spent in the ethanol-paired chamber was seen. MRT treatment at both doses showed better effect than CLN in preventing the development of preference in CPP test. These findings indicate a potential therapeutic use and better profile of mirtazapine over clonidine in improving memory, as well as in alleviating depression, anxiety and craving associated

  6. Time-dependent negative reinforcement of ethanol intake by alleviation of acute withdrawal.

    PubMed

    Cunningham, Christopher L; Fidler, Tara L; Murphy, Kevin V; Mulgrew, Jennifer A; Smitasin, Phoebe J

    2013-02-01

    Drinking to alleviate the symptoms of acute withdrawal is included in diagnostic criteria for alcoholism, but the contribution of acute withdrawal relief to high alcohol intake has been difficult to model in animals. Ethanol dependence was induced by passive intragastric ethanol infusions in C57BL/6J (B6) and DBA/2J (D2) mice; nondependent control animals received water infusions. Mice were then allowed to self-administer ethanol or water intragastrically. The time course of acute withdrawal was similar to that produced by chronic ethanol vapor exposure in mice, reaching a peak at 7 to 9 hours and returning to baseline within 24 hours; withdrawal severity was greater in D2 than in B6 mice (experiment 1). Postwithdrawal delays in initial ethanol access (1, 3, or 5 days) reduced the enhancement in later ethanol intake normally seen in D2 (but not B6) mice allowed to self-infuse ethanol during acute withdrawal (experiment 2). The postwithdrawal enhancement of ethanol intake persisted over a 5-day abstinence period in D2 mice (experiment 3). D2 mice allowed to drink ethanol during acute withdrawal drank more ethanol and self-infused more ethanol than nondependent mice (experiment 4). Alcohol access during acute withdrawal increased later alcohol intake in a time-dependent manner, an effect that may be related to a genetic difference in sensitivity to acute withdrawal. This promising model of negative reinforcement encourages additional research on the mechanisms underlying acute withdrawal relief and its role in determining risk for alcoholism. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  7. Caffeinated Alcohol Consumption Profiles and Associations with Use Severity and Outcome Expectancies

    PubMed Central

    Lau-Barraco, Cathy; Milletich, Robert J.; Linden, Ashley N.

    2014-01-01

    Growing evidence suggests that the consumption of caffeinated alcoholic beverages (CAB) may be riskier than alcohol alone. Efforts to identify patterns of CAB use and the correlates of such drinking patterns could further our conceptualization of and intervention for this health issue. Consequently, the current study aimed to (1) identify distinct classes of CAB users, (2) examine differences between classes on measures of alcohol and caffeine problems, and (3) compare distinct classes of CAB users on caffeine and alcohol outcome expectancies. Participants were 583 (31% men) undergraduate students from a psychology research pool. Latent profile analysis models were derived using four indicators: CAB use quantity, CAB use frequency, alcohol use quantity, and alcohol use frequency. Finding revealed four classes of drinkers: High Alcohol/High CAB (6.00%), High Alcohol/Moderate CAB (5.15%), High Alcohol/Low CAB (22.99%), and Low Alcohol/Low CAB (65.87%). The Low Alcohol/Low CAB class reported the lowest relative levels of caffeine dependence symptoms, caffeine withdrawal, alcohol use problems, and heavy episodic drinking frequency. Further, results indicated differential expectancy endorsement based on use profiles. CAB users in the High Alcohol/Low CAB class endorsed more positive alcohol expectancies than the Low Alcohol/Low CAB group. Those in the High Alcohol/High CAB class endorsed stronger withdrawal symptoms caffeine expectancies than all other classes. Inclusion of substance-specific expectancies into larger theoretical frameworks in future work of CAB use may be beneficial. Findings may inform intervention efforts for those at greatest risk related to CAB consumption. PMID:24210683

  8. Caffeinated alcohol consumption profiles and associations with use severity and outcome expectancies.

    PubMed

    Lau-Barraco, Cathy; Milletich, Robert J; Linden, Ashley N

    2014-01-01

    Growing evidence suggests that the consumption of caffeinated alcoholic beverages (CAB) may be riskier than alcohol alone. Efforts to identify patterns of CAB use and the correlates of such drinking patterns could further our conceptualization of and intervention for this health issue. Consequently, the current study aimed to (1) identify distinct classes of CAB users, (2) examine differences between classes on measures of alcohol and caffeine problems, and (3) compare distinct classes of CAB users on caffeine and alcohol outcome expectancies. Participants were 583 (31% men) undergraduate students from a psychology research pool. Latent profile analysis models were derived using four indicators: CAB use quantity, CAB use frequency, alcohol use quantity, and alcohol use frequency. Finding revealed four classes of drinkers: High Alcohol/High CAB (6.00%), High Alcohol/Moderate CAB (5.15%), High Alcohol/Low CAB (22.99%), and Low Alcohol/Low CAB (65.87%). The Low Alcohol/Low CAB class reported the lowest relative levels of caffeine dependence symptoms, caffeine withdrawal, alcohol use problems, and heavy episodic drinking frequency. Further, results indicated differential expectancy endorsement based on use profiles. CAB users in the High Alcohol/Low CAB class endorsed more positive alcohol expectancies than the Low Alcohol/Low CAB group. Those in the High Alcohol/High CAB class endorsed stronger withdrawal symptom caffeine expectancies than all other classes. Inclusion of substance-specific expectancies into larger theoretical frameworks in future work of CAB use may be beneficial. Findings may inform intervention efforts for those at greatest risk related to CAB consumption. © 2013.

  9. Identification of a QTL in Mus musculus for Alcohol Preference, Withdrawal, and Ap3m2 Expression Using Integrative Functional Genomics and Precision Genetics

    PubMed Central

    Bubier, Jason A.; Jay, Jeremy J.; Baker, Christopher L.; Bergeson, Susan E.; Ohno, Hiroshi; Metten, Pamela; Crabbe, John C.; Chesler, Elissa J.

    2014-01-01

    Extensive genetic and genomic studies of the relationship between alcohol drinking preference and withdrawal severity have been performed using animal models. Data from multiple such publications and public data resources have been incorporated in the GeneWeaver database with >60,000 gene sets including 285 alcohol withdrawal and preference-related gene sets. Among these are evidence for positional candidates regulating these behaviors in overlapping quantitative trait loci (QTL) mapped in distinct mouse populations. Combinatorial integration of functional genomics experimental results revealed a single QTL positional candidate gene in one of the loci common to both preference and withdrawal. Functional validation studies in Ap3m2 knockout mice confirmed these relationships. Genetic validation involves confirming the existence of segregating polymorphisms that could account for the phenotypic effect. By exploiting recent advances in mouse genotyping, sequence, epigenetics, and phylogeny resources, we confirmed that Ap3m2 resides in an appropriately segregating genomic region. We have demonstrated genetic and alcohol-induced regulation of Ap3m2 expression. Although sequence analysis revealed no polymorphisms in the Ap3m2-coding region that could account for all phenotypic differences, there are several upstream SNPs that could. We have identified one of these to be an H3K4me3 site that exhibits strain differences in methylation. Thus, by making cross-species functional genomics readily computable we identified a common QTL candidate for two related bio-behavioral processes via functional evidence and demonstrate sufficiency of the genetic locus as a source of variation underlying two traits. PMID:24923803

  10. Response to CPAP Withdrawal in Patients with Mild Versus Severe Obstructive Sleep Apnea/Hypopnea Syndrome

    PubMed Central

    Young, Laura R.; Taxin, Zachary H.; Norman, Robert G.; Walsleben, Joyce A.; Rapoport, David M.; Ayappa, Indu

    2013-01-01

    Background: Patients with obstructive sleep apnea/hypopnea syndrome (OSAHS), even those generally compliant with CPAP therapy, often intermittently discontinue CPAP. Study Objective: Examine the impact of CPAP withdrawal on sleep, sleep disordered breathing (SDB), and daytime function in subjects with varying severity of OSAHS. Patients and Interventions: Forty-two subjects (26M/16 F) with OSAHS (AHI4% = 45.2 ± 35.5/h pretreatment) on CPAP for 4 months were evaluated on the second night of CPAP withdrawal. Sleep architecture, SDB indices, and subjective/objective daytime function were assessed pretreatment, on CPAP therapy, and after CPAP withdrawal. Comparisons were made between pretreatment and CPAP withdrawal for the entire group, and for subgroups of mild/moderate (AHI4% < 30/h, n = 22) and severe (AHI4% > 30/h, n = 20) SDB. Results: Overall, and for mild/moderate subjects, SDB indices returned to pretreatment values on CPAP withdrawal but with fewer apneas and more hypopneas/RERAs. For severe SDB, the event frequency (AI, AHI4%, and RDI) was lower and O2 desaturation was improved on CPAP withdrawal. Across SDB severity, sleep architecture showed lower %REM (15.6% vs 12.9%, P = 0.009) on the CPAP withdrawal compared to pretreatment. Stanford Sleepiness Score, MSLT, and PVT measures were not significantly different between pretreatment and CPAP withdrawal. Conclusions: Over a wide range of SDB severity CPAP withdrawal results in recurrence of SDB, albeit with less severe O2 desaturation. Subjective/objective daytime function returned to pretreatment levels. Sleep architecture changes on CPAP withdrawal (acute SDB) may reflect reduced sleep pressure compared to pretreatment chronic SDB. Our data suggest detrimental effects of even brief withdrawal of CPAP in subjects with both mild and severe OSAHS. Citation: Young LR; Taxin ZH; Norman RG; Walsleben JA; Rapoport DM; Ayappa I. Response to CPAP withdrawal in patients with mild versus severe obstructive sleep apnea

  11. Using the AUDIT-PC to predict alcohol withdrawal in hospitalized patients.

    PubMed

    Pecoraro, Anna; Ewen, Edward; Horton, Terry; Mooney, Ruth; Kolm, Paul; McGraw, Patty; Woody, George

    2014-01-01

    Alcohol withdrawal syndrome (AWS) occurs when alcohol-dependent individuals abruptly reduce or stop drinking. Hospitalized alcohol-dependent patients are at risk. Hospitals need a validated screening tool to assess withdrawal risk, but no validated tools are currently available. To examine the admission Alcohol Use Disorders Identification Test-(Piccinelli) Consumption (AUDIT-PC) ability to predict the subsequent development of AWS among hospitalized medical-surgical patients admitted to a non-intensive care setting. Retrospective case–control study of patients discharged from the hospital with a diagnosis of AWS. All patients with AWS were classified as presenting with AWS or developing AWS later during admission. Patients admitted to an intensive care setting and those missing AUDIT-PC scores were excluded from analysis. A hierarchical (by hospital unit) logistic regression was performed and receiver-operating characteristics were examined on those developing AWS after admission and randomly selected controls. Because those diagnosing AWS were not blinded to the AUDIT-PC scores, a sensitivity analysis was performed. The study cohort included all patients age ≥18 years admitted to any medical or surgical units in a single health care system from 6 October 2009 to 7 October 2010. After exclusions, 414 patients were identified with AWS. The 223 (53.9 %) who developed AWS after admission were compared to 466 randomly selected controls without AWS. An AUDIT-PC score ≥4 at admission provides 91.0 % sensitivity and 89.7 % specificity (AUC=0.95; 95 % CI, 0.94–0.97) for AWS, and maximizes the correct classification while resulting in 17 false positives for every true positive identified. Performance remained excellent on sensitivity analysis (AUC=0.92; 95 % CI, 0.90–0.93). Increasing AUDIT-PC scores were associated with an increased risk of AWS (OR=1.68, 95 % CI 1.55–1.82, p<0.001). The admission AUDIT-PC score is an excellent discriminator of AWS and could be

  12. Identification of a QTL in Mus musculus for alcohol preference, withdrawal, and Ap3m2 expression using integrative functional genomics and precision genetics.

    PubMed

    Bubier, Jason A; Jay, Jeremy J; Baker, Christopher L; Bergeson, Susan E; Ohno, Hiroshi; Metten, Pamela; Crabbe, John C; Chesler, Elissa J

    2014-08-01

    Extensive genetic and genomic studies of the relationship between alcohol drinking preference and withdrawal severity have been performed using animal models. Data from multiple such publications and public data resources have been incorporated in the GeneWeaver database with >60,000 gene sets including 285 alcohol withdrawal and preference-related gene sets. Among these are evidence for positional candidates regulating these behaviors in overlapping quantitative trait loci (QTL) mapped in distinct mouse populations. Combinatorial integration of functional genomics experimental results revealed a single QTL positional candidate gene in one of the loci common to both preference and withdrawal. Functional validation studies in Ap3m2 knockout mice confirmed these relationships. Genetic validation involves confirming the existence of segregating polymorphisms that could account for the phenotypic effect. By exploiting recent advances in mouse genotyping, sequence, epigenetics, and phylogeny resources, we confirmed that Ap3m2 resides in an appropriately segregating genomic region. We have demonstrated genetic and alcohol-induced regulation of Ap3m2 expression. Although sequence analysis revealed no polymorphisms in the Ap3m2-coding region that could account for all phenotypic differences, there are several upstream SNPs that could. We have identified one of these to be an H3K4me3 site that exhibits strain differences in methylation. Thus, by making cross-species functional genomics readily computable we identified a common QTL candidate for two related bio-behavioral processes via functional evidence and demonstrate sufficiency of the genetic locus as a source of variation underlying two traits. Copyright © 2014 by the Genetics Society of America.

  13. Incidence rates of admissions associated with alcohol withdrawal syndrome in Spain: Analysis of minimum basic data set 1999-2010.

    PubMed

    Gómez-Méndez, Raquel; Monte-Secades, Rafael; Ventura-Valcárcel, Pablo; Rabuñal-Rey, Ramón; Guerrero-Sande, Héctor; Chamorro-Fernández, Antonio J; Pértega-Díaz, Sonia

    2017-12-20

    There are no data on the incidence of admissions associated with alcohol withdrawal syndrome (AWS) or about its trend over time in Spain. To analyze the characteristics, incidence rates and trends over time of hospital admissions associated with AWS in Spanish public hospitals. Analysis from the Spanish public hospitals minimum basic data set of hospital admissions with AWS (CIE9-MC 291.81), alcohol withdrawal delirium (CIE9-MC 291.0) and alcohol withdrawal hallucinosis (CIE9-MC 291.3), since 1999 to 2010. We identified 56,395 admissions associated with AWS. Mean age was 50.9 (SD 12.5) and 88% were male. The most frequent admission department was Internal Medicine (24.9%). The mean hospital stay was 12.6 days (SD 14.4) and mortality was 4.7%; 62.6% of cases developed AWS during an admission for another reason, mostly due to alcohol-related pathologies. Secondary diagnoses in patients hospitalized for AWS were related to alcohol consumption in more than half of the cases. The incidence rate of admissions associated with AWS in Spain remained stable from 1999 to 2010, with a small decline in the last 3 years of the period. The communities with the highest incidence were the Canary Islands, the Balearic Islands and Galicia. The incidence rate of admissions associated with AWS in Spanish public hospitals in the period 1999-2010 has remained stable with slight changes. There are differences in the incidence of AWS among the different autonomous communities. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  14. Repeated diazepam administration reversed working memory impairments and glucocorticoid alterations in the prefrontal cortex after short but not long alcohol-withdrawal periods.

    PubMed

    Dominguez, G; Henkous, N; Pierard, C; Belzung, C; Mons, N; Beracochea, Daniel

    2018-04-30

    The study was designed to assess whether repeated administration of diazepam (Valium®, Roche)-a benzodiazepine exerting an agonist action on GABA A receptors-may alleviate both the short (1 week, 1W) and long-term (6 weeks, 6W) deleterious effects of alcohol withdrawal occurring after chronic alcohol consumption (6 months; 12% v/v) in C57/BL6 male mice. More pointedly, we first evidenced that 1W and 6W alcohol-withdrawn mice exhibited working memory deficits in a sequential alternation task, associated with sustained exaggerated corticosterone rise and decreased pCREB levels in the prefrontal cortex (PFC). In a subsequent experiment, diazepam was administered i.p. for 9 consecutive days (1 injection/day) during the alcohol withdrawal period at decreasing doses ranging from 1.0 mg/kg to 0.25 mg/kg. Diazepam was not detected in the blood of withdrawn mice at the time of memory testing, occurring 24 hours after the last diazepam injection. Repeated diazepam administration significantly improved alternation rates and normalized levels of glucocorticoids and pCREB activity in the PFC in 1W but not in 6W withdrawn mice. Thus, repeated diazepam administration during the alcohol-withdrawal period only transitorily canceled out the working memory impairments and glucocorticoid alterations in the PFC of alcohol-withdrawn animals.

  15. DIFFERENTIAL EFFECTS OF SINGLE VERSUS REPEATED ALCOHOL WITHDRAWAL ON THE EXPRESSION OF ENDOCANNABINOID SYSTEM-RELATED GENES IN THE RAT AMYGDALA

    PubMed Central

    Serrano, Antonia; Rivera, Patricia; Pavon, Francisco J.; Decara, Juan; Suárez, Juan; de Fonseca, Fernando Rodriguez; Parsons, Loren H.

    2011-01-01

    Background Endogenous cannabinoids such as anandamide and 2-arachidonoylglycerol (2-AG) exert important regulatory influences on neuronal signaling, participate in short- and long-term forms of neuroplasticity, and modulate stress responses and affective behavior in part through the modulation of neurotransmission in the amygdala. Alcohol consumption alters brain endocannabinoid levels, and alcohol dependence is associated with dysregulated amygdalar function, stress responsivity and affective control. Methods The consequence of long-term alcohol consumption on the expression of genes related to endocannabinoid signaling was investigated using quantitative RT-PCR analyses of amygdala tissue. Two groups of ethanol-exposed rats were generated by maintenance on an ethanol liquid diet (10%): one group received continuous access to ethanol for 15 days, while the second group was given intermittent access to the ethanol diet (5 days/week for 3 weeks). Control subjects were maintained on an isocaloric ethanol-free liquid diet. To provide an initial profile of acute withdrawal amygdala tissue was harvested following either 6 or 24 hours of ethanol withdrawal. Results Acute ethanol withdrawal was associated with significant changes in mRNA expression for various components of the endogenous cannabinoid system in the amygdala. Specifically, reductions in mRNA expression for the primary clearance routes for anandamide and 2-AG (FAAH and MAGL, respectively) were evident, as were reductions in mRNA expression for CB1, CB2 and GPR55 receptors. Although similar alterations in FAAH mRNA were evident following either continuous or intermittent ethanol exposure, alterations in MAGL and cannabinoid receptor-related mRNA (e.g. CB1, CB2, GPR55) were more pronounced following intermittent exposure. In general, greater withdrawal-associated deficits in mRNA expression were evident following 24 versus 6 hours of withdrawal. No significant changes in mRNA expression for enzymes involved in

  16. 27 CFR 19.1002 - Prohibited uses, transfers, and withdrawals.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... person shall withdraw, use, sell, or otherwise dispose of distilled spirits (including fuel alcohol... withdraws, uses, sells or otherwise disposes of distilled spirits (including fuel alcohol) produced under... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Prohibited uses, transfers...

  17. Aggression and increased glutamate in the mPFC during withdrawal from intermittent alcohol in outbred mice.

    PubMed

    Hwa, Lara S; Nathanson, Anna J; Shimamoto, Akiko; Tayeh, Jillian K; Wilens, Allison R; Holly, Elizabeth N; Newman, Emily L; DeBold, Joseph F; Miczek, Klaus A

    2015-08-01

    Disrupted social behavior, including occasional aggressive outbursts, is characteristic of withdrawal from long-term alcohol (EtOH) use. Heavy EtOH use and exaggerated responses during withdrawal may be treated using glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonists. The current experiments explore aggression and medial prefrontal cortex (mPFC) glutamate as consequences of withdrawal from intermittent access to EtOH and changes in aggression and mPFC glutamate caused by NMDAR antagonists memantine and ketamine. Swiss male mice underwent withdrawal following 1-8 weeks of intermittent access to 20 % EtOH. Aggressive and nonaggressive behaviors with a conspecific were measured 6-8 h into EtOH withdrawal after memantine or ketamine (0-30 mg/kg, i.p.) administration. In separate mice, extracellular mPFC glutamate after memantine was measured during withdrawal using in vivo microdialysis. At 6-8 h withdrawal from EtOH, mice exhibited more convulsions and aggression and decreased social contact compared to age-matched water controls. Memantine, but not ketamine, increased withdrawal aggression at the 5-mg/kg dose in mice with a history of 8 weeks of EtOH but not 1 or 4 weeks of EtOH or in water drinkers. Tonic mPFC glutamate was higher during withdrawal after 8 weeks of EtOH compared to 1 week of EtOH or 8 weeks of water. Five milligrams per kilogram of memantine increased glutamate in 8-week EtOH mice, but also in 1-week EtOH and water drinkers. These studies reveal aggressive behavior as a novel symptom of EtOH withdrawal in outbred mice and confirm a role of NMDARs during withdrawal aggression and for disrupted social behavior.

  18. Aggression and increased glutamate in the mPFC during withdrawal from intermittent alcohol in outbred mice

    PubMed Central

    Hwa, Lara S.; Nathanson, Anna J.; Shimamoto, Akiko; Tayeh, Jillian K.; Wilens, Allison R.; Holly, Elizabeth N.; Newman, Emily L.; DeBold, Joseph F.; Miczek, Klaus A.

    2015-01-01

    Rationale Disrupted social behavior, including occasional aggressive outbursts, is characteristic of withdrawal from long-term alcohol (EtOH) use. Heavy EtOH use and exaggerated responses during withdrawal may be treated using glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonists. Objectives The current experiments explore aggression and medial prefrontal cortex (mPFC) glutamate as consequences of withdrawal from intermittent access to EtOH, and changes in aggression and mPFC glutamate caused by NMDAR antagonists memantine and ketamine. Methods Swiss male mice underwent withdrawal following 1-8 weeks of intermittent access to 20% EtOH. Aggressive and non-aggressive behaviors with a conspecific were measured 6-8 h into EtOH withdrawal after memantine or ketamine (0-30 mg/kg, i.p.) administration. In separate mice, extracellular mPFC glutamate after memantine was measured during withdrawal using in vivo microdialysis. Results At 6-8 h withdrawal from EtOH, mice exhibited more convulsions and aggression, and decreased social contact compared to age-matched water controls. Memantine, but not ketamine, increased withdrawal aggression at the 5 mg/kg dose in mice with a history of 8 weeks EtOH but not 1 or 4 weeks of EtOH or in water drinkers. Tonic mPFC glutamate was higher during withdrawal after 8 weeks EtOH compared to 1 week EtOH or 8 weeks water. Five mg/kg memantine increased glutamate in 8 week EtOH mice, but also in 1 week EtOH and water drinkers. Conclusions These studies reveal aggressive behavior as a novel symptom of EtOH withdrawal in outbred mice and confirm a role of NMDARs during withdrawal aggression and for disrupted social behavior. PMID:25899790

  19. Concurrent validity of the Alcohol Use Disorders Identification Test (AUDIT) and AUDIT zones in defining levels of severity among out-patients with alcohol dependence in the COMBINE study.

    PubMed

    Donovan, Dennis M; Kivlahan, Daniel R; Doyle, Suzanne R; Longabaugh, Richard; Greenfield, Shelly F

    2006-12-01

    To examine among alcohol-dependent out-patient clients the concurrent validity of the Alcohol Use Disorders Identification Test (AUDIT) total score and 'zones' suggested by the World Health Organization for defining levels of severity of alcohol use problems. Participants were classified into AUDIT zones (AUDIT total score = 8-15, 16-19, 20-40) and compared on measures of demographics, treatment goals, alcohol consumption, alcohol-related consequences, severity of dependence, physiological dependence, tolerance, withdrawal and biomarkers of alcohol use. Eleven out-patient academic clinical research centers across the United States. Participants Alcohol dependent individuals (n = 1335) entering out-patient treatment in the Combined Pharmacotherapies and Behavioral Interventions (COMBINE) study. The AUDIT was administered as part of an initial screening. Baseline measures used for concurrent validation included the Structured Clinical Interview for Diagnostic and Statistical Manual, 4th edition (DSM-IV) Disorders, the Alcohol Dependence Scale, the Drinker Inventory of Consequences, the Obsessive-Compulsive Drinking Scale, the University of Rhode Island Change Assessment, the Thoughts about Abstinence Scale, the Form-90, %carbohydrate-deficient transferrin and gamma-glutamyl transferase. Findings Indicators of severity of dependence and alcohol-related problems increased linearly with total score and differed significantly across AUDIT zones. The highest zone, with scores of 20 and above, was markedly different with respect to severity from the other two zones and members of this group endorsed an abstinence goal more strongly. The AUDIT total score is a brief measure that appears to provide an index of severity of dependence in a sample of alcohol-dependent individuals seeking out-patient treatment, extending its potential utility beyond its more traditional role as a screening instrument in general populations.

  20. [Aggression and restlessness following baclofen overdose: the narrow line between intoxication and withdrawal symptoms].

    PubMed

    de Witte, L D; Dekker, D; Veraart, J; Kromkamp, M; Kaasjager, K; Vinkers, C H

    2016-01-01

    Baclofen is increasingly prescribed for alcohol dependency. Subsequently, the risk of self-intoxication with this medicinal product is increasing. A 23-year-old man with a history of alcohol dependence was admitted to our hospital after self-intoxication with 2700 mg baclofen and 330 mg mirtazapine. Respiratory insufficiency as a result of the baclofen intoxication required intubation and admission to the ICU. During the first day, despite the use of sedatives, the patient became intermittently agitated and aggressive. In the following days, he developed severe delirium, probably due to baclofen withdrawal. The reintroduction of baclofen quickly resolved these symptoms. In the case of baclofen, in practice it is difficult to differentiate between intoxication and withdrawal. To prevent potentially severe withdrawal symptoms, we recommend reintroduction of baclofen when the first signs of restlessness and agitation arise following intoxication.

  1. Sex Differences in the Effect of Finasteride on Acute Ethanol Withdrawal Severity in C57BL/6J and DBA/2J Mice

    PubMed Central

    Gorin-Meyer, Rebecca E.; Wiren, Kristine M.; Tanchuck, Michelle A.; Long, Season L.; Yoneyama, Naomi; Finn, Deborah A.

    2007-01-01

    The neurosteroid allopregnanolone (ALLO) is a potent positive modulator of γ-aminobutyric acidA (GABAA) receptors that can modulate ethanol (EtOH) withdrawal. The 5α-reductase inhibitor finasteride can block the formation of ALLO and other GABAergic neurosteroids and also reduce certain effects of EtOH. Treatment with finasteride during chronic EtOH exposure decreased EtOH withdrawal severity and blood EtOH concentrations (BECs), suggesting an additional effect of finasteride on EtOH pharmacokinetics. Thus, the purpose of the present study was to determine the effect of finasteride on acute EtOH withdrawal severity, to minimize the effect of finasteride on EtOH metabolism. Male and female C57BL/6J and DBA/2J mice received a pretreatment of finasteride (50 mg/kg i.p.) or vehicle 24 hours prior to an injection of EtOH (4 g/kg i.p.) or saline. Handling-induced convulsions (HICs) were scored at baseline, and then over a 24 hr period after EtOH or saline injection. In another experiment, plasma estradiol and corticosterone levels were assessed at selected time points (0, 2, 8, and 24 hrs). In a final study, retro-orbital blood samples were collected at 30, 60, 120, and 240 minutes post-EtOH administration to access finasteride’s effects on EtOH clearance parameters. Pretreatment with finasteride increased acute EtOH withdrawal severity in female C57BL/6J and DBA/2J mice but decreased withdrawal severity in male mice of both strains. Finasteride did not alter BECs, EtOH clearance, estradiol, or corticosterone concentrations in a manner that appeared to contribute to the sex difference in finasteride’s effect on acute EtOH withdrawal severity. These findings suggest that male and female C57BL/6J and DBA/2J mice differ in their sensitivity to changes in ALLO or other GABAergic neurosteroid levels during acute EtOH withdrawal. Sex differences in the modulation of GABAergic 5α-reduced steroids may be an important consideration in understanding and developing

  2. Acute Ethanol Withdrawal Impairs Contextual Learning and Enhances Cued Learning

    PubMed Central

    Tipps, Megan E.; Raybuck, Jonathan D.; Buck, Kari J.; Lattal, K. Matthew

    2014-01-01

    Background Alcohol affects many of the brain regions and neural processes that support learning and memory, and these effects are thought to underlie, at least in part, the development of addiction. Although much work has been done regarding the effects of alcohol intoxication on learning and memory, little is known about the effects of acute withdrawal from a single alcohol exposure. Methods We assess the effects of acute ethanol withdrawal (6 h post-injection with 4 g/kg ethanol) on two forms of fear conditioning (delay and trace fear conditioning) in C57BL/6J and DBA/2J mice. The influence of a number of experimental parameters (pre- and post-training withdrawal exposure; foreground/background processing; training strength; non-associative effects) is also investigated. Results Acute ethanol withdrawal during training had a bidirectional effect on fear conditioned responses, decreasing contextual responses and increasing cued responses. These effects were apparent for both trace and delay conditioning in DBA/2J mice and for trace conditioning in C57BL/6J mice; however, C57BL/6J mice were selectively resistant to the effects of acute withdrawal on delay cued responses. Conclusions Our results show that acute withdrawal from a single, initial ethanol exposure is sufficient to alter long-term learning in mice. In addition, the differences between the strains and conditioning paradigms used suggest that specific learning processes can be differentially affected by acute withdrawal in a manner that is distinct from the reported effects of both alcohol intoxication and withdrawal following chronic alcohol exposure. Thus, our results suggest a unique effect of acute alcohol withdrawal on learning and memory processes. PMID:25684050

  3. [Compulsory hospitalisation of patients suffering from severe drug or alcohol addiction].

    PubMed

    Höppener, P E; Godschalx-Dekker, J A; van de Wetering, B J M

    2013-01-01

    Psychiatrists treating patients with drug and alcohol addiction currently consider these afflicions to be mental disorders. If patients are so mentally disturbed that they are a danger to themselves or others, then compulsory hospitalisation seems to be an acceptable treatment option. However, it would seem that at present this solution is not normal practice in addiction care. To describe the indications for compulsory hospitalisation when mental disorders associated with addiction and withdrawal cause risks and dangers. Discussion of the indications for compulsory enforced hospitalisation supported by literature. Compulsory hospitalisation is based on the acceptance of the principle that addiction and substance abuse are mental disorders. Indications for emergency hospitalisation include intoxications, acute withdrawal symptoms and other disorders associated with substance use. Indications for longer-term measures are (self)-protection, societal isolation and the need to protect other people from danger. Factors influencing the decision-making process regarding emergency hospitalisation are motivation and treatment perspectives, mental incompetence, contraindications and conflicts between criminal law and patients’ rights. Compulsory hospitalisation deserves serious consideration as the ultimate step in treatment of intoxication, drug and alcohol dependence and withdrawal symptoms. In addition, emergency hospitalisation can be a way of averting danger, facilitating diagnosis and motivating abstinence or at least a reduction in substance use.

  4. Outpatient alcohol withdrawal management for Aboriginal and Torres Strait Islander peoples.

    PubMed

    Brett, Jonathan; Lawrence, Leanne; Ivers, Rowena; Conigrave, Kate

    2014-08-01

    There is concern from within Aboriginal and Torres Strait Islander communities about the lack of access to alcohol withdrawal management ('detox') services. Outpatient detox is described within national Australian guidelines as a safe option for selected drinkers. However, uncertainly exists as to how suited Aboriginal and Torres Strait Islander peoples are to this approach. 
 Consultations were conducted with stakeholders of four health services providing outpatient detox for Aboriginal and Torres Strait Islander peoples in NSW. Thematic analysis was performed to determine elements perceived as important for success. Key themes that emerged were individual engagement, flexibility, assessment of suitability, Aboriginal staff and community engagement, practical support, counselling, staff education and support, coping with relapse and contingency planning. 
 There is a need to improve access to alcohol detox services for Aboriginal and Torres Strait Islander peoples. The outpatient setting seems to be a feasible and safe environment to provide this kind of service for selected drinkers.

  5. Conceptualizing withdrawal-induced escalation of alcohol self-administration as a learned, plasticity-dependent process

    PubMed Central

    Walker, Brendan M.

    2013-01-01

    This article represents one of five contributions focusing on the topic “Plasticity and neuroadaptive responses within the extended amygdala in response to chronic or excessive alcohol exposure” that were developed by awardees participating in the Young Investigator Award Symposium at the “Alcoholism and Stress: A Framework for Future Treatment Strategies” conference in Volterra, Italy on May 3–6, 2011 that was organized/chaired by Drs. Antonio Noronha and Fulton Crews and sponsored by the National Institute on Alcohol Abuse and Alcoholism. This review discusses the dependence-induced neuroadaptations in affective systems that provide a basis for negative reinforcement learning and presents evidence demonstrating that escalated alcohol consumption during withdrawal is a learned, plasticity-dependent process. The review concludes by identifying changes within extended amygdala dynorphin/kappa-opioid receptor systems that could serve as the foundation for the occurrence of negative reinforcement processes. While some evidence contained herein may be specific to alcohol dependence-related learning and plasticity, much of the information will be of relevance to any addictive disorder involving negative reinforcement mechanisms. Collectively, the information presented within this review provides a framework to assess the negative reinforcing effects of alcohol in a manner that distinguishes neuroadaptations produced by chronic alcohol exposure from the actual plasticity that is associated with negative reinforcement learning in dependent organisms. PMID:22459874

  6. Severe Carisoprodol Withdrawal After a 14-Year Addiction and Acute Overdose.

    PubMed

    Vo, Kathy T; Horng, Howard; Smollin, Craig G; Benowitz, Neal L

    2017-05-01

    Carisoprodol, a centrally acting muscle relaxant with a high abuse potential, has barbiturate-like properties at the GABA-A receptor, leading to central nervous system depression and desired effects. Its tolerance and dependence has been previously demonstrated in an animal model, and withdrawal has been described in several recent case reports. Many cases can be effectively managed with a short course of benzodiazepines or antipsychotic agents. However, abrupt cessation in a patient with a history of long-term and high-dose carisoprodol abuse may result in symptoms that are more difficult for providers to treat. We present a case of a 34-year-old man with a long history of carisoprodol abuse who was found unresponsive after having ingested 7.5 grams of carisoprodol. He was intubated and admitted to the intensive care unit. He was given propofol, dexmedetomidine, fentanyl, ketamine, lorazepam, midazolam, quetiapine, and haloperidol, some at high-dose infusions, before his agitation and ventilator asynchrony could be controlled. His improvement coincided with the addition of carisoprodol and phenobarbital to his treatment regimen. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Trends show increasing emergency department presentations for drug-related disorders and treatment. This case highlights an uncommon case of carisoprodol withdrawal that may be encountered by emergency physicians, and demonstrates that benzodiazepines may not be sufficient to suppress severe withdrawal symptoms. Treatment with carisoprodol and phenobarbital provided additional benefit and can be considered in cases of severe carisoprodol withdrawal. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Sex Differences in Acute Ethanol Withdrawal Severity After Adrenalectomy and Gonadectomy in WSP and WSR Mice

    PubMed Central

    Strong, Moriah N.; Kaufman, Katherine R.; Crabbe, John C.; Finn, Deborah A.

    2009-01-01

    Recent findings suggest that the ability of ethanol (EtOH) to increase the levels of neurosteroids with potent γ-aminobutyric acid (GABA)ergic properties can influence measures of EtOH sensitivity. Earlier studies determined that removal of the adrenals and gonads diminished the steroidogenic effect of EtOH and significantly increased acute EtOH withdrawal severity in two inbred mouse strains that differed in withdrawal severity, suggesting the contribution of anticonvulsant GABAergic steroids to acute withdrawal in intact animals. Thus, the goal of the present studies was to investigate the consequence of steroid removal on acute EtOH withdrawal through excision of the adrenals and gonads, in another genetic animal model of EtOH withdrawal differences, the Withdrawal Seizure-Prone (WSP) and -Resistant (WSR) selected lines. Male and female WSP and WSR mice underwent surgical removal of the adrenals and gonads or no organ removal (SHAM). One to two weeks later, baseline handling-induced convulsions (HICs) were assessed, mice were given a 4 g/kg dose of ethanol, and HICs were measured hourly for 12 hours and then at 24 hours. The combination surgery significantly increased EtOH withdrawal in WSP and WSR female mice, as measured by area under the curve (AUC) and peak HIC scores. AUC was significantly positively correlated with plasma corticosterone levels and significantly negatively correlated with progesterone levels. In contrast, surgical status did not alter withdrawal severity in male WSP and WSR mice. Overall, the increase in acute ethanol withdrawal severity in female WSP and WSR mice following adrenalectomy and gonadectomy corroborate our recent evidence that withdrawal from a high dose of EtOH can be modulated by anticonvulsant steroids produced in the periphery. PMID:19671463

  8. Relationship of nicotine deprivation and indices of alcohol use behavior to implicit alcohol and cigarette approach cognitions in smokers.

    PubMed

    Cohn, Amy; Ehlke, Sarah; Cobb, Caroline O

    2017-04-01

    Alcohol and smoking frequently co-occur and alcohol is a primary trigger for smoking behavior and relapse back to smoking. This study examined whether several indices of alcohol use behavior and consequences of use would be associated with changes in implicit alcohol-approach versus implicit cigarette-approach cognitions under cigarette deprived and non-deprived cognitions in 109 smokers who drank at risky or non-risky levels. An Implicit Association Task (IAT) measured how quickly respondents paired alcohol and cigarette pictures with approach and avoid words. Regression analyses examined the associations of quantity/frequency, proportion heavy drinking days, number of DSM-IV alcohol use disorder (AUD) symptoms, and risky drinking status to IAT scores under deprived conditions, controlling for IAT order effects, non-deprived IAT score, and deprived cigarette craving and withdrawal. Interactions with craving and withdrawal intensity were also examined. Results showed a significant positive association between proportion of heavy drinking days and stronger alcohol-approach than cigarette-approach motivations when deprived. There was also a conditional association of AUD symptoms to alcohol-approach motivations among respondents reporting more intense withdrawal when deprived. Alcohol quantity and frequency, as well as risky drinking status were unrelated to change in IAT scores. Findings suggest that cigarette deprivation may magnify motivation to drink, rather than smoke, among smokers who engage in more frequent bouts of heavy drinking and who report more alcohol-related problems. Results also show relative momentary and unconscious "preference" or choice for alcohol over cigarettes in some high-risk smokers, when cigarette craving and withdrawal are high. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Epidemiological and sociodemographic factors associated with complicated alcohol withdrawal syndrome.

    PubMed

    Monte-Secades, R; Blanco-Soto, M; Díaz-Peromingo, J A; Sanvisens-Bergé, A; Martín-González, M C; Barbosa, A; Rosón-Hernández, B; Tejero-Delgado, M A; Puerta-Louro, R; Rabuñal-Rey, R

    2017-10-01

    To analyse the influence of epidemiological and sociodemographic factors in complicated alcohol withdrawal syndrome (AWS). A multicentre, observational prospective study was conducted on consecutively added patients with AWS hospitalised in internal medicine departments. We recorded sociodemographic, epidemiological, clinical and progression data. Complicated AWS was defined as that which progressed with seizures or delirium tremens. We studied 228 episodes of AWS in 219 patients. The mean age was 54.5 years (SD, 11.5), and 90.8% were men. AWS was the cause for hospitalisation in 39.9% of the patients. Some 27.1% of the cases presented seizures, and 32.4% presented delirium tremens. The daily quantity of alcohol ingested was 17.8 standard drink units (SD, 21.4), with 16.6 years of dependence (SD, 11.3). The pattern of alcohol abuse was regular in 82.8% of the patients. Some 38.4% of the patients were married or had a partner, and 45.6% had children. Some 72.7% of the patients were unemployed or retired. Some 68.5% had only completed primary studies. Some 4.8% consumed cannabis, 5.2% consumed cocaine and 3% consumed opioids. The independent variables related to complicated AWS were consumption of a drug other than alcohol (OR, 5.3; 95% CI 1.5-18.7), low education level (OR, 3.4; 95% CI 1.6-7.3) and hospitalisation for AWS (OR, 2.9; 95% CI 1.5-5.6). The model's receiver operating characteristic area was 0.718 (95% CI 0.643-0.793). Concomitant drug abuse and a low educational level could help identify patients at risk of complicated AWS. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  10. Withdrawal strategies for outpatients

    PubMed Central

    Mezciems, Edgar

    1996-01-01

    This article discusses outpatient withdrawal strategies for patients addicted to alcohol, benzodiazepines, barbiturates, and opiates and describes some practical ways to support recovery. PMID:8828877

  11. 27 CFR 19.532 - Withdrawals of spirits for use in wine production.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... use in wine production. 19.532 Section 19.532 Alcohol, Tobacco Products and Firearms ALCOHOL AND... Withdrawals Withdrawal of Spirits Without Payment of Tax § 19.532 Withdrawals of spirits for use in wine production. Wine spirits may be withdrawn to a bonded wine cellar without payment of tax for use in wine...

  12. Behavioral and biochemical effects of ethanol withdrawal in zebrafish.

    PubMed

    da Silva Chaves, Suianny Nayara; Felício, Gabriel Rocha; Costa, Bruna Patrícia Dutra; de Oliveira, Witallo Etevaldo Araújo; Lima-Maximino, Monica Gomes; Siqueira Silva, Diógenes Henrique de; Maximino, Caio

    2018-06-01

    Chronic alcohol use induces adaptations and toxicity that can induce symptoms of anxiety, autonomic hyperarousal, and epileptic seizures when alcohol is removed (withdrawal syndrome). Zebrafish has recently gained wide attention as a behavioral model to study the neurobehavioral effects of acute and chronic alcohol use, including withdrawal. The literature, however, is very contradictory on findings regarding withdrawal effects, with some studies reporting increased anxiety, while others report no effect. A meta-analytic approach was taken to find the sources of this heterogeneity, and ethanol concentration during exposure and exposure duration were found to be the main sources of variation. A conceptual replication was also made using continuous exposure for 16 days in waterborne ethanol (0.5%) and assessing anxiety-like behavior in the light/dark test after 60 min withdrawal. Withdrawal was shown to reduce preference for darkness, consistent with decreased anxiety, but to increase risk assessment, consistent with increased anxiety. Animals were also subjected to the withdrawal protocol and injected with pilocarpine in a sub-convulsive dose to assess susceptibility to epileptic seizure-like behavior. The protocol was sufficient to increase susceptibility to epileptic seizure-like behavior in animals exposed to ethanol. Finally, withdrawal also decreased catalase activity in the brain, but not in the head kidney, suggesting mechanisms associated with the behavioral effects of ethanol withdrawal. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Genetic variation of the ghrelin signaling system in females with severe alcohol dependence.

    PubMed

    Landgren, Sara; Jerlhag, Elisabet; Hallman, Jarmila; Oreland, Lars; Lissner, Lauren; Strandhagen, Elisabeth; Thelle, Dag S; Zetterberg, Henrik; Blennow, Kaj; Engel, Jörgen A

    2010-09-01

    Central ghrelin signaling is required for the rewarding effects of alcohol in mice. Because ghrelin is implied in other addictive behaviors such as eating disorders and smoking, and because there is co-morbidity between these disorders and alcohol dependence, the ghrelin signaling system could be involved in mediating reward in general. Furthermore, in humans, single nucleotide polymorphisms (SNPs) and haplotypes of the pro-ghrelin gene (GHRL) and the ghrelin receptor gene (GHSR) have previously been associated with increased alcohol consumption and increased body weight. Known gender differences in plasma ghrelin levels prompted us to investigate genetic variation of the ghrelin signaling system in females with severe alcohol dependence (n = 113) and in a selected control sample of female low-consumers of alcohol from a large cohort study in southwest Sweden (n = 212). Six tag SNPs in the GHRL (rs696217, rs3491141, rs4684677, rs35680, rs42451, and rs26802) and four tag SNPs in the GHSR (rs495225, rs2232165, rs572169, and rs2948694) were genotyped in all individuals. We found that one GHRL haplotype was associated with reports of paternal alcohol dependence as well as with reports of withdrawal symptoms in the female alcohol-dependent group. Associations with 2 GHSR haplotypes and smoking were also shown. One of these haplotypes was also negatively associated with BMI in controls, while another haplotype was associated with having the early-onset, more heredity-driven, type 2 form of alcohol dependence in the patient group. Taken together, the genes encoding the ghrelin signaling system cannot be regarded as major susceptibility genes for female alcohol dependence, but is, however, involved in paternal heritability and may affect other reward- and energy-related factors such as smoking and BMI.

  14. Role of cortical alpha-2 adrenoceptors in alcohol withdrawal-induced depression and tricyclic antidepressants

    PubMed Central

    Getachew, Bruk; Hauser, Sheketha R.; Csoka, Antonei B.; Taylor, Robert E.; Tizabi, Yousef

    2017-01-01

    Introduction Although a role for alpha-2 adrenoceptors (alpha-2 ARs) in alcohol use disorder (AUD) and depression is suggested, very little information on a direct interaction between alcohol and these receptors is available. Methods In this study adult female Wistar and Wistar-Kyoto (WKY) rats, a putative animal model of depression, were exposed to alcohol vapor 3 h daily for 10 days (blood alcohol concentration ~150 mg%) followed by daily injection of 10 mg/kg of imipramine (IMP, a selective norepinephrine NE/serotonin reuptake inhibitor) or nomifensine (NOMI, a selective NE/dopamine reuptake inhibitor). On day 11 animals were tested for open field locomotor activity (OFLA) and forced swim test (FST) and were sacrificed 2 h later for measurement of alpha-2 ARs densities in the frontal cortex and hippocampus using [3H]RX 821002 as the specific ligand. Results Chronic alcohol treatment increased the immobility in the FST, without affecting OFLA in both Wistar and WKY rats, suggesting induction of depressive-like behavior in Wistar rats and an exacerbation of this behavior in WKY rats. Alcohol treatment also resulted in an increase in cortical but not hippocampal alpha-2 ARs densities in both Wistar and WKY rats. The behavioral effects of alcohol were completely blocked by IMP and NOMI and the neurochemical effects (increases in alpha-2 ARs) were significantly attenuated by both drugs in both strains. Conclusions The results suggest a role for cortical alpha-2 ARs in alcohol withdrawal-induced depression and that selective subtype antagonists of these receptors may be of adjunct therapeutic potential in AUD-depression co-morbidity. PMID:28414989

  15. 27 CFR 20.161 - Withdrawals under permit.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Withdrawals under permit. 20.161 Section 20.161 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS DISTRIBUTION AND USE OF DENATURED ALCOHOL AND RUM Operations by Dealers and Users of Specially Denatured Spirit...

  16. Platelet rebound effect of alcohol withdrawal and wine drinking in rats. Relation to tannins and lipid peroxidation.

    PubMed

    Ruf, J C; Berger, J L; Renaud, S

    1995-01-01

    We investigated in rats fed a purified diet for 2 and 4 months whether wine drinking was associated with the rebound effect on thrombin-induced platelet aggregation observed after alcohol withdrawal. With 6% ethanol drinking or its equivalent in red or white wine, platelet aggregation was reduced similarly by 70% when the animals drank the alcoholic beverages up to the venipuncture. Depriving the rats of alcoholic beverages for 18 hours was associated with an increase in the platelet response of 124% in those receiving 6% ethanol, of 46% with white wine but a decrease of 59% in those with red wine. The protective effect of red wine on platelets could be reproduced by tannins (procyanidins) extracted from grape seeds or red wine and added to 6% ethanol, but not by glycerol or wine without alcohol. That was related to inhibition of the alcohol-induced lipid peroxidation as shown by the lowering of conjugated dienes, lipid peroxides, and the increase in vitamin E in plasma. Owing to tannins, the platelets of rats drinking red wine did not exhibit the rebound effect observed hours after alcohol drinking, eventually associated with sudden death and stroke in humans.

  17. 27 CFR 19.728 - Withdrawal of spirits.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... premises of an alcohol fuel plant, the proprietor must render the spirits unfit for beverage use as... alcohol fuel plant premises if they will be used exclusively for fuel. (26 U.S.C. 5181, 5214) ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Withdrawal of spirits. 19...

  18. 27 CFR 19.996 - Withdrawal of spirits.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... alcohol fuel plant, they must be rendered unfit for beverage use as provided in this subpart. Spirits rendered unfit for beverage use (fuel alcohol) may be withdrawn free of tax from plant premises exclusively... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Withdrawal of spirits. 19...

  19. The use of a food supplementation with D-phenylalanine, L-glutamine and L-5-hydroxytriptophan in the alleviation of alcohol withdrawal symptoms.

    PubMed

    Jukić, Tomislav; Rojc, Bojan; Boben-Bardutzky, Darja; Hafner, Mateja; Ihan, Alojz

    2011-12-01

    We described the use of a food supplementation with D-phenylalanine, L-glutamine and L-5-hydroxytriptophan in the alleviation of alcohol withdrawal symptoms in patients starting a detoxification therapy. Since abstinence from ethanol causes a hypodopaminergic and a hypoopioidergic environment in the reword system circuits, manifesting with withdrawal symptoms, food supplements that contains D-phenylalanine a peptidase inhibitor (of opioide inactivation) and L-amino-acids (for dopamine synthesis) were used to replenish a lack in neurotransmitters and alleviate the symptoms of alcohol withdrawal. 20 patients suffering from alcohol addictions starting a detoxification therapy have been included in a prospective, randomized, double blind study. The patients have been randomly devided in two groups. One group recieved for a period of 40 days a food supplement containing D-phenylalanine, L-glutamine and L-5-hydroxytriptophan (investigation group), and the control (placebo) group. On the first day of hospitalization the patients performed a SCL-90-R test, and blood samples were taken for measuring liver enzymes, total bilirubin, unbound cortisol and lymphocyte populations. The same was done on the 40th day of hospitalization. During the therapy a significant decrease in SCL-90-R psychiatric symptoms scores and a significant increase in CD4 lymphocyte count was observed in the investigation group. The cortisol values were significantly, but equally decreased in both groups, the same was with the liver enzymes and the total bilirubin values. We conclude that abstinence causes a major stress for the patients. The use of food supplement containing D-phenylalanine, L-glutamine and L-5-hydroxytriptophan alleviates the withdrawal symptoms and causes a rise in CD4 lymphocyte population, but it dose not affect the serum cortisol levels, which are probably more affected by liver inflammation and the liver restitution.

  20. A lack of association between severity of nicotine withdrawal and individual differences in compensatory nicotine self-administration in rats

    PubMed Central

    Harris, Andrew C.; Pentel, Paul R.; Burroughs, Danielle; Staley, Mylissa D.; LeSage, Mark G.

    2013-01-01

    Rationale Compensatory smoking may represent an adverse consequence of smoking reduction or the use of reduced nicotine tobacco products. Factors contributing to individual variability in compensation are poorly understood. Objective To examine whether severity of nicotine withdrawal as measured by elevated intracranial self-stimulation (ICSS) thresholds is related to individual differences in compensatory nicotine self-administration (NSA) following unit dose reduction. Methods Rats were trained for ICSS and NSA (0.06 mg/kg/inf). After stabilization, effects of reducing the nicotine unit dose to 0.03 mg/kg/inf were examined. Following reacquisition of NSA (0.06 mg/kg/inf), effects of antagonist-precipitated withdrawal and saline extinction (spontaneous withdrawal) were examined. Results Reducing the NSA unit dose produced partial compensation as indicated by increased infusion rates but a 35% mean decrease in daily nicotine intake. Magnitude of compensation varied considerably among rats. Dose reduction did not elicit withdrawal in rats as a group, although there were substantial increases in ICSS thresholds in some animals. Intracranial self-stimulation thresholds were consistently elevated during precipitated and spontaneous withdrawal, confirming that rats were nicotine-dependent. Individual differences in compensation were not correlated with changes in ICSS thresholds during dose reduction, precipitated withdrawal, or spontaneous withdrawal. In a secondary analysis, greater precipitated withdrawal severity predicted greater initial nicotine-seeking during extinction. Conclusions Severity of nicotine withdrawal was not related to the degree of compensation in this protocol. These data do not support a role for nicotine withdrawal in individual differences in compensation during reduced nicotine exposure, but do suggest that withdrawal may contribute to nicotine-seeking during early abstinence. PMID:21494791

  1. 27 CFR 19.585 - Production and withdrawal records.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... records. 19.585 Section 19.585 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL DISTILLED SPIRITS PLANTS Records and Reports Production Records § 19.585 Production and withdrawal records. (a) Production of spirits. The following rules apply...

  2. 27 CFR 19.585 - Production and withdrawal records.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... records. 19.585 Section 19.585 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL DISTILLED SPIRITS PLANTS Records and Reports Production Records § 19.585 Production and withdrawal records. (a) Production of spirits. The following rules apply...

  3. Accomplishing much in a short time: use of a rapid improvement event to redesign the assessment and treatment of patients with alcohol withdrawal.

    PubMed

    Sankoff, Jeffrey; Taub, Julie; Mintzer, David

    2013-01-01

    The use of Lean tools for quality improvement and process refinement is gaining acceptance in many health care institutions. Traditionally, these tools are used to apply incremental changes to established processes in order to reduce waste and improve quality. In this article, the authors describe a novel Lean methodology, the Rapid Improvement Event (RIE), used in a unique way to develop a new treatment protocol for a specific medical condition: alcohol withdrawal. The RIE allowed for the collaboration of a multidisciplinary group of providers invested in the success of a new protocol for alcohol withdrawal that spans areas from the emergency department to the inpatient ward at an inner-city safety net hospital. It also allowed for the definition of measures for its success once it is implemented.

  4. Anterior Cingulate Cortex Contributes to Alcohol Withdrawal- Induced and Socially Transferred Hyperalgesia.

    PubMed

    Smith, Monique L; Walcott, Andre T; Heinricher, Mary M; Ryabinin, Andrey E

    2017-01-01

    Pain is often described as a "biopsychosocial" process, yet social influences on pain and underlying neural mechanisms are only now receiving significant experimental attention. Expression of pain by one individual can be communicated to nearby individuals by auditory, visual, and olfactory cues. Conversely, the perception of another's pain can lead to physiological and behavioral changes in the observer, which can include induction of hyperalgesia in "bystanders" exposed to "primary" conspecifics in which hyperalgesia has been induced directly. The current studies were designed to investigate the neural mechanisms responsible for the social transfer of hyperalgesia in bystander mice housed and tested with primary mice in which hyperalgesia was induced using withdrawal (WD) from voluntary alcohol consumption. Male C57BL/6J mice undergoing WD from a two-bottle choice voluntary alcohol-drinking procedure served as the primary mice. Mice housed in the same room served as bystanders. Naïve, water-drinking controls were housed in a separate room. Immunohistochemical mapping identified significantly enhanced Fos immunoreactivity (Fos-ir) in the anterior cingulate cortex (ACC) and insula (INS) of bystander mice compared to naïve controls, and in the dorsal medial hypothalamus (DMH) of primary mice. Chemogenetic inactivation of the ACC but not primary somatosensory cortex reversed the expression of hyperalgesia in both primary and bystander mice. These studies point to an overlapping neural substrate for expression of socially transferred hyperalgesia and that expressed during alcohol WD.

  5. Preclinical Evaluation of Riluzole: Assessments of Ethanol Self-Administration and Ethanol Withdrawal Symptoms

    PubMed Central

    Besheer, Joyce; Lepoutre, Veronique; Hodge, Clyde W.

    2010-01-01

    Background Many of the neurobehavioral effects of ethanol are mediated by inhibition of excitatory N-methyl-d-aspartate (NMDA) and enhancement of inhibitory γ-amino-butyric-acid (GABA) receptor systems. There is growing interest in drugs that alter these systems as potential medications for problems associated with alcoholism. The drug riluzole, approved for treatment of amyotrophic lateral sclerosis (ALS), inhibits NMDA and enhances GABAA receptor system activity. This study was designed to determine the preclinical efficacy of riluzole to modulate ethanol self-administration and withdrawal. Methods Male C57BL/6J mice were trained to lever press on a concurrent fixed-ratio 1 schedule of ethanol (10% v/v) versus water reinforcement during daily 16-hour sessions. Riluzole (1 to 40 mg/kg, IP) was evaluated on ethanol self-administration after acute and chronic (2 week) treatment. To determine if riluzole influences ethanol withdrawal-associated seizures, mice were fed an ethanol-containing or control liquid diet for 18 days. The effects of a single injection of riluzole (30 mg/kg) were examined on handling-induced convulsions after ethanol withdrawal. Results Acute riluzole (30 and 40 mg/kg) reduced ethanol self-administration during the first 4 hours of the session, which corresponds to the known pharmacokinetics of this drug. Ethanol self-administration was also reduced by riluzole after chronic treatment. Riluzole (30 mg/kg) significantly decreased the severity of ethanol-induced convulsions 2 hours after ethanol withdrawal. Conclusions These results demonstrate that riluzole decreases ethanol self-administration and may reduce ethanol withdrawal severity in mice. Thus, riluzole may have utility in the treatment of problems associated with alcoholism. PMID:19426166

  6. Circadian wheel-running activity during withdrawal from chronic intermittent ethanol exposure in mice

    PubMed Central

    Logan, Ryan W.; Seggio, Joseph A.; Robinson, Stacy L.; Richard, Gregory R.; Rosenwasser, Alan M.

    2010-01-01

    Alcohol withdrawal is associated with affective-behavioral disturbances in both human alcoholics and in animal models. In general, these phenomena are potentiated by increased alcohol exposure duration and by prior withdrawal episodes. Previous studies have also reported locomotor hypoactivity during ethanol withdrawal in rats and mice, but only in novel test environments, not in the home-cage. In the present study, we examined the effects of withdrawal from chronic intermittent ethanol (CIE) vapor exposure on the level and circadian periodicity of wheel-running activity in C57BL/6J mice. CIE treatment resulted in reductions in wheel-running activity relative to plain-air controls that persisted for about one week after withdrawal. Analysis of circadian waveforms indicated that reduced activity occurred throughout the night phase, but that daily activity patterns were otherwise unaltered. CIE failed to alter free-running circadian period or phase in animals maintained under constant darkness. These results show that ethanol withdrawal can result in locomotor hypoactivity even in the habitual, home-cage environment, and suggest that withdrawal-related reductions in wheel-running activity may reflect the specific motivational significance of this behavior. PMID:20682191

  7. Implementing managed alcohol programs in hospital settings: A review of academic and grey literature.

    PubMed

    Brooks, Hannah L; Kassam, Shehzad; Salvalaggio, Ginetta; Hyshka, Elaine

    2018-04-01

    People with severe alcohol use disorders are at increased risk of poor acute-care outcomes, in part due to difficulties maintaining abstinence from alcohol while hospitalised. Managed alcohol programs (MAP), which administer controlled doses of beverage alcohol to prevent withdrawal and stabilise drinking patterns, are one strategy for increasing adherence to treatment, and improving health outcomes for hospital inpatients with severe alcohol use disorders. Minimal research has examined the implementation of MAPs in hospital settings. We conducted a scoping review to describe extant literature on MAPs in community settings, as well as the therapeutic provision of alcohol to hospital inpatients, to assess the feasibility of implementing formal MAPs in hospital settings and identify knowledge gaps requiring further study. Four academic and 10 grey literature databases were searched. Evidence was synthesised using quantitative and qualitative approaches. Forty-two studies met review inclusion criteria. Twenty-eight examined the administration of alcohol to hospital inpatients, with most reporting positive outcomes related to prevention or treatment of alcohol withdrawal. Fourteen studies examined MAPs in the community and reported that they help stabilise drinking patterns, reduce alcohol-related harms and facilitate non-judgemental health and social care. MAPs in the community have been well described and research has documented effective provision of alcohol in hospital settings for addressing withdrawal. Implementing MAPs as a harm reduction approach in hospital settings is potentially feasible. However, there remains a need to build off extant literature and develop and evaluate standardised MAP protocols tailored to acute-care settings. © 2018 Australasian Professional Society on Alcohol and other Drugs.

  8. Incidence and impact of withdrawal of life-sustaining therapies in clinical trials of severe traumatic brain injury: A systematic review.

    PubMed

    Leblanc, Guillaume; Boutin, Amélie; Shemilt, Michèle; Lauzier, François; Moore, Lynne; Potvin, Véronique; Zarychanski, Ryan; Archambault, Patrick; Lamontagne, François; Léger, Caroline; Turgeon, Alexis F

    2018-06-01

    Background Most deaths following severe traumatic brain injury follow decisions to withdraw life-sustaining therapies. However, the incidence of the withdrawal of life-sustaining therapies and its potential impact on research data interpretation have been poorly characterized. The aim of this systematic review was to assess the reporting and the impact of withdrawal of life-sustaining therapies in randomized clinical trials of patients with severe traumatic brain injury. Methods We searched Medline, Embase, Cochrane Central, BIOSIS, and CINAHL databases and references of included trials. All randomized controlled trials published between January 2002 and August 2015 in the six highest impact journals in general medicine, critical care medicine, and neurocritical care (total of 18 journals) were considered for eligibility. Randomized controlled trials were included if they enrolled adult patients with severe traumatic brain injury (Glasgow Coma Scale ≤ 8) and reported data on mortality. Our primary objective was to assess the proportion of trials reporting the withdrawal of life-sustaining therapies in a publication. Our secondary objectives were to describe the overall mortality rate, the proportion of deaths following the withdrawal of life-sustaining therapies, and to assess the impact of the withdrawal of life-sustaining therapies on trial results. Results From 5987 citations retrieved, we included 41 randomized trials (n = 16,364, ranging from 11 to 10,008 patients). Overall mortality was 23% (range = 3%-57%). Withdrawal of life-sustaining therapies was reported in 20% of trials (8/41, 932 patients in trials) and the crude number of deaths due to the withdrawal of life-sustaining therapies was reported in 17% of trials (7/41, 884 patients in trials). In these trials, 63% of deaths were associated with the withdrawal of life-sustaining therapies (105/168). An analysis carried out by imputing a 4% differential rate in instances of withdrawal of life

  9. Influence of Volatile Anesthesia on the Release of Glutamate and other Amino Acids in the Nucleus Accumbens in a Rat Model of Alcohol Withdrawal: A Pilot Study

    PubMed Central

    Seidemann, Thomas; Spies, Claudia; Morgenstern, Rudolf; Wernecke, Klaus-Dieter; Netzhammer, Nicolai

    2017-01-01

    Background Alcohol withdrawal syndrome is a potentially life-threatening condition, which can occur when patients with alcohol use disorders undergo general anesthesia. Excitatory amino acids, such as glutamate, act as neurotransmitters and are known to play a key role in alcohol withdrawal syndrome. To understand this process better, we investigated the influence of isoflurane, sevoflurane, and desflurane anesthesia on the profile of excitatory and inhibitory amino acids in the nucleus accumbens (NAcc) of alcohol-withdrawn rats (AWR). Methods Eighty Wistar rats were randomized into two groups of 40, pair-fed with alcoholic or non-alcoholic nutrition. Nutrition was withdrawn and microdialysis was performed to measure the activity of amino acids in the NAcc. The onset time of the withdrawal syndrome was first determined in an experiment with 20 rats. Sixty rats then received isoflurane, sevoflurane, or desflurane anesthesia for three hours during the withdrawal period, followed by one hour of elimination. Amino acid concentrations were measured using chromatography and results were compared to baseline levels measured prior to induction of anesthesia. Results Glutamate release increased in the alcohol group at five hours after the last alcohol intake (p = 0.002). After 140 min, desflurane anesthesia led to a lower release of glutamate (p < 0.001) and aspartate (p = 0.0007) in AWR compared to controls. GABA release under and after desflurane anesthesia was also significantly lower in AWR than controls (p = 0.023). Over the course of isoflurane anesthesia, arginine release decreased in AWR compared to controls (p < 0.001), and aspartate release increased after induction relative to controls (p20min = 0.015 and p40min = 0.006). However, amino acid levels did not differ between the groups as a result of sevoflurane anesthesia. Conclusions Each of three volatile anesthetics we studied showed different effects on excitatory and inhibitory amino acid concentrations. Under

  10. Influence of Volatile Anesthesia on the Release of Glutamate and other Amino Acids in the Nucleus Accumbens in a Rat Model of Alcohol Withdrawal: A Pilot Study.

    PubMed

    Seidemann, Thomas; Spies, Claudia; Morgenstern, Rudolf; Wernecke, Klaus-Dieter; Netzhammer, Nicolai

    2017-01-01

    Alcohol withdrawal syndrome is a potentially life-threatening condition, which can occur when patients with alcohol use disorders undergo general anesthesia. Excitatory amino acids, such as glutamate, act as neurotransmitters and are known to play a key role in alcohol withdrawal syndrome. To understand this process better, we investigated the influence of isoflurane, sevoflurane, and desflurane anesthesia on the profile of excitatory and inhibitory amino acids in the nucleus accumbens (NAcc) of alcohol-withdrawn rats (AWR). Eighty Wistar rats were randomized into two groups of 40, pair-fed with alcoholic or non-alcoholic nutrition. Nutrition was withdrawn and microdialysis was performed to measure the activity of amino acids in the NAcc. The onset time of the withdrawal syndrome was first determined in an experiment with 20 rats. Sixty rats then received isoflurane, sevoflurane, or desflurane anesthesia for three hours during the withdrawal period, followed by one hour of elimination. Amino acid concentrations were measured using chromatography and results were compared to baseline levels measured prior to induction of anesthesia. Glutamate release increased in the alcohol group at five hours after the last alcohol intake (p = 0.002). After 140 min, desflurane anesthesia led to a lower release of glutamate (p < 0.001) and aspartate (p = 0.0007) in AWR compared to controls. GABA release under and after desflurane anesthesia was also significantly lower in AWR than controls (p = 0.023). Over the course of isoflurane anesthesia, arginine release decreased in AWR compared to controls (p < 0.001), and aspartate release increased after induction relative to controls (p20min = 0.015 and p40min = 0.006). However, amino acid levels did not differ between the groups as a result of sevoflurane anesthesia. Each of three volatile anesthetics we studied showed different effects on excitatory and inhibitory amino acid concentrations. Under desflurane anesthesia, both glutamate

  11. Alcohol use disorders and current pharmacological therapies: the role of GABAA receptors

    PubMed Central

    Liang, Jing; Olsen, Richard W

    2014-01-01

    Alcohol use disorders (AUD) are defined as alcohol abuse and alcohol dependence, which create large problems both for society and for the drinkers themselves. To date, no therapeutic can effectively solve these problems. Understanding the underlying mechanisms leading to AUD is critically important for developing effective and safe pharmacological therapies. Benzodiazepines (BZs) are used to reduce the symptoms of alcohol withdrawal syndrome. However, frequent use of BZs causes cross-tolerance, dependence, and cross-addiction to alcohol. The FDA-approved naltrexone and acamprosate have shown mixed results in clinical trials. Naltrexone is effective to treat alcohol dependence (decreased length and frequency of drinking bouts), but its severe side effects, including withdrawal symptoms, are difficult to overcome. Acamprosate showed efficacy for treating alcohol dependence in European trials, but two large US trials have failed to confirm the efficacy. Another FDA-approved medication, disulfiram, does not diminish craving, and it causes a peripheral neuropathy. Kudzu is the only natural medication mentioned by the National Institute on Alcohol Abuse and Alcoholism, but its mechanisms of action are not yet established. It has been recently shown that dihydromyricetin, a flavonoid purified from Hovenia, has unique effects on GABAA receptors and blocks ethanol intoxication and withdrawal in alcoholic animal models. In this article, we review the role of GABAA receptors in the treatment of AUD and currently available and potentially novel pharmacological agents. PMID:25066321

  12. Modulation of ethanol withdrawal-induced anxiety-like behavior during later withdrawals by treatment of early withdrawals with benzodiazepine/gamma-aminobutyric acid ligands.

    PubMed

    Knapp, Darin J; Overstreet, David H; Breese, George R

    2005-04-01

    Anxiety states, including those arising during acute or protracted withdrawal periods, may be precipitating factors in alcoholic relapse. Given the cyclical nature of ethanol withdrawal associated with repeated cycles of ethanol intake and abstinence in a pattern that often spans years, meaningful attempts to model ethanol withdrawal-associated anxiety should incorporate cycled ethanol treatments. The studies reported herein examined the effects of gamma-aminobutyric acid-modulating drugs on social interaction behavior-an established model of anxiety-in rats exposed to repeated cycles of ethanol treatment and withdrawal. Rats were exposed to 8 to 12 g/kg/day ethanol during three 7-day dietary cycles (5 days on ethanol diet followed by 2 days on control diet). Ethanol was administered either at hour 4 of withdrawal after cessation of each of the first 2 ethanol cycles or during the final withdrawal only. In other groups, the early withdrawals were treated with alphaxalone, diazepam, PK11159, or flumazenil to block anxiety-like behavior during an untreated later (third) withdrawal. The benzodiazepine inverse agonist DMCM (methyl-6, 7-dymerhoxy-4-ethyl-beta-carboline-3-carboxylate) was also given repeatedly to determine whether it would sensitize anxiety-like behavior during a future withdrawal. Finally, the effects of all drugs on deficits in locomotor behavior were assessed. Pretreatment of earlier withdrawals with alphaxalone, diazepam, ethanol, or flumazenil reduced social interaction deficits during a later withdrawal, but pretreatment with PK11195 did not. In contrast, DMCM administered in lieu of early withdrawals increased social interaction deficits during an untreated later withdrawal. Locomotor deficits were significantly reversed only by the acute ethanol and diazepam treatment during the final withdrawal. Single-dose administration of drugs that enhance or diminish activity at benzodiazepine-gamma-aminobutyric acid- receptors during earlier withdrawals

  13. Critical thoughts on current rodent models for evaluating potential treatments of alcohol addiction and withdrawal

    PubMed Central

    Ripley, Tamzin L; Stephens, David N

    2011-01-01

    Despite years of neurobiological research that have helped to identify potential therapeutic targets, we do not have a reliable pharmacological treatment for alcoholism. There are a range of possible explanations for this failure, including arguments that alcoholism is a spectrum disorder and that different population subtypes may respond to different treatments. This view is supported by categorisations such as early- and late-onset alcoholism, whilst multifactorial genetic factors may also alter responsivity to pharmacological agents. Furthermore, experience of alcohol withdrawal may play a role in future drinking in a way that may distinguish alcoholism from other forms of addiction. Additionally, our neurobiological models, based largely upon results from rodent studies, may not mimic specific aspects of the human condition and may reflect different underlying phenomena and biological processes from the clinical pattern. As a result, potential treatments may be targeting inappropriate aspects of alcohol-related behaviours. Instead, we suggest a more profitable approach is (a) to identify well-defined intermediate behavioural phenotypes in human experimental models that reflect defined aspects of the human clinical disorder and (b) to develop animal models that are homologous with those phenotypes in terms of psychological processes and underlying neurobiological mechanisms. This review describes an array of animal models currently used in the addiction field and what they tell us about alcoholism. We will then examine how established pharmacological agents have been developed using only a limited number of these models, before describing some alternative novel approaches to achieving homology between animal and human experimental measures. LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4 PMID:21470204

  14. [Characteristics of alcohol withdrawal delirium in surgical patients and recommendations for treatment].

    PubMed

    Naber, M; Franz, W; Overbeck, W

    1991-02-01

    An alcohol withdrawal syndrome affects the patient in a 'vulnerable phase' either after an operation or posttraumatically. It can be shown pathophysiologically, that the symptoms are caused by a hyperactivity of the central sympathetic nervous system and a disbalance of the neurotransmitters. As for these complex symptoms, a multi-layered treatment is required. We report on our experiences with 23 patients who were treated in our intensive care unit. The treatment included a benzo-diazepine and a drug effecting central alpha 2-receptors. Only three of these patients had to be intubated or ventilated. Because of the induced bradycardia monitor observation was required in all cases. The patients could be wakened up at any time and thus were co-operative for basic care. One patient died of pulmonary embolism, a second patient died of cardiovascular failure as a consequence of cardiac insufficiency.

  15. Severe Central Sleep Apnea Associated With Chronic Baclofen Therapy: A Case Series.

    PubMed

    Olivier, Pierre-Yves; Joyeux-Faure, Marie; Gentina, Thibaut; Launois, Sandrine H; d'Ortho, Marie Pia; Pépin, Jean-Louis; Gagnadoux, Frédéric

    2016-05-01

    Baclofen, a gamma-aminobutyric acid-B agonist with muscle-relaxant properties, is widely used in patients with severe spasticity. In animals, baclofen has been shown to decrease respiratory drive. In humans, however, use of baclofen at the standard dose did not significantly impair sleep-disordered breathing in a susceptible population of snorers. Recently, there has been increasing interest in the role of baclofen for the treatment of alcohol dependence. We describe severe central sleep apnea (CSA) in four patients with none of the conditions commonly associated with CSA who were receiving chronic baclofen therapy for alcohol withdrawal. In one patient, baclofen withdrawal was associated with a complete resolution of CSA. Three patients were treated by adaptive servo-ventilation while continuing their treatment with baclofen. Given the increasing number of patients receiving baclofen for alcohol withdrawal treatment, physicians should be aware that these patients might be affected by severe CSA. Future studies are required to determine the mechanisms, prevalence, and treatment modalities of sleep-disordered breathing associated with baclofen usage. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  16. Pharmacotherapeutic Treatment of Alcohol Dependence: An Overview

    ERIC Educational Resources Information Center

    Graves, Erin; Goodwin, Lloyd R., Jr.

    2008-01-01

    Pharmacotherapy medications can reduce the likelihood of relapse, decrease craving intensity and severity of withdrawal symptoms, and bolster the likelihood of achieving and maintaining recovery goals for many individuals seeking recovery from alcohol dependence. An overview of the benefits and concerns of integrating pharmacotherapeutic…

  17. Opiate and opioid withdrawal

    MedlinePlus

    ... opiate withdrawal; Oxycontin - opiate withdrawal; Hydrocodone - opiate withdrawal; Detox - opiates; Detoxification - opiates ... facilities set up to help people with detoxification (detox). In a regular hospital, if symptoms are severe. ...

  18. Severity of Withdrawal Symptoms, Plasma Oxytocin Levels, and Treatment Outcome in Heroin Users Undergoing Acute Withdrawal.

    PubMed

    Nikolaou, Kakia; Kapoukranidou, Dorothea; Ndungu, Samuel; Floros, Georgios; Kovatsi, Leda

    2017-01-01

    Pre-clinical studies show that, following chronic opioid exposure, oxytocin neurons exhibit over-excitation upon withdrawal, causing an increase in oxytocin brain and plasma levels. Relevant clinical data on humans are scarce. This study investigates the opioid withdrawal stress effect on oxytocin plasma levels in humans. We evaluated 57 male chronic heroin users in a residential detoxification program. We determined plasma oxytocin levels by ELISA and measured the stress effects of withdrawal using the COWS scale for opioid withdrawal, the VAS scale for craving, and the Hamilton scales for anxiety and depression on the second day of admission. Out of the 57 patients enrolled in the study, 27 completed the 21-day program, while the remaining 30 dropped out prior to completion. Plasma oxytocin levels were significantly higher in those individuals who dropped out than in those who completed the program. Participants who dropped out at some stage scored higher in the COWS, VAS-Craving, and Hamilton-anxiety scales, indicating a higher stress and explaining the higher oxytocin levels. In addition, plasma oxytocin levels correlated positively with the scores achieved in the COWS and Hamilton-anxiety scales. Higher withdrawal stress levels are associated with higher plasma oxytocin levels and early treatment discharge.

  19. 27 CFR 19.585 - Production and withdrawal records.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... records. 19.585 Section 19.585 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS DISTILLED SPIRITS PLANTS Records and Reports Production Records § 19.585 Production and withdrawal records. (a) Production of spirits. The following rules apply...

  20. 27 CFR 22.111 - Withdrawals under permit.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., DEPARTMENT OF THE TREASURY LIQUORS DISTRIBUTION AND USE OF TAX-FREE ALCOHOL Withdrawal and Receipt of Tax... distilled spirits plant or, under the provisions of 26 U.S.C. 5688(a)(2)(B), receive alcohol from the... its permit, or amended permit, to a distilled spirits plant for the “initial order” from that...

  1. Does alcohol involvement increase the severity of intimate partner violence?

    PubMed

    McKinney, Christy M; Caetano, Raul; Rodriguez, Lori A; Okoro, Ngozi

    2010-04-01

    Most studies that have examined alcohol use immediately prior to intimate partner violence (IPV) have been limited to male-to-female partner violence (MFPV) and are subject to a number of methodological limitations. We add new information concerning the relationship between alcohol involvement and severity of IPV, MFPV, and female-to-male partner violence (FMPV). We analyzed data from a 1995 U.S. national population-based survey of couples > or = 18 years old. We examined 436 couples who reported IPV and had information on alcohol involvement with IPV. We measured IPV using a revised Conflict Tactics Scale, Form R that asked respondents about 11 violent behaviors in the past year. Respondents were classified into mutually exclusive categories as having experienced mild only or mild + severe ("severe") IPV, MFPV or FMPV. Respondents were also asked if they or their partner were drinking at the time the violent behavior occurred and were classified as exposed to IPV with or without alcohol involvement. We estimated proportions, odds ratios, 95% confidence intervals, and p-values of the proposed associations, accounting for the complex survey design. Overall, 30.2% of couples who reported IPV reported alcohol involved IPV; 69.8% reported no alcohol involvement. In adjusted analyses, those reporting severe (vs. mild only) IPV were more than twice as likely to report alcohol involvement. In adjusted analyses, those reporting severe (vs. mild) MFPV or FMPV were more likely to report female but not male alcohol involvement. Though estimates were positive and strong, most confidence intervals were compatible with a wide range of estimates including no association. Our findings suggest alcohol involvement of either or both in the couple increases the risk of severe IPV. Our findings also suggest female alcohol use may play an important role in determining the severity of IPV, MFPV or FMPV.

  2. Pharmacologically induced alcohol craving in treatment seeking alcoholics correlates with alcoholism severity, but is insensitive to acamprosate

    PubMed Central

    Umhau, John C; Schwandt, Melanie L; Usala, Julie; Geyer, Christopher; Singley, Erick; George, David T; Heilig, Markus

    2011-01-01

    Modulation of alcohol craving induced by challenge stimuli may predict the efficacy of new pharmacotherapies for alcoholism. We evaluated two pharmacological challenges, the α2-adrenergic antagonist yohimbine, which reinstates alcohol seeking in rats, and the serotonergic compound meta-chlorophenylpiperazine (mCPP), previously reported to increase alcohol craving in alcoholics. To assess the predictive validity of this approach, the approved alcoholism medication acamprosate was evaluated for its ability to modulate challenge-induced cravings. A total of 35 treatment seeking alcohol dependent inpatients in early abstinence were randomized to placebo or acamprosate (2997 mg daily). Following two weeks of medication, subjects underwent three challenge sessions with yohimbine, mCPP or saline infusion under double blind conditions, carried out in counterbalanced order, and separated by at least 5 days. Ratings of cravings and anxiety, as well as biochemical measures were obtained. In all, 25 subjects completed all three sessions and were included in the analysis. Cravings were modestly, but significantly higher following both yohimbine and mCPP challenge compared with saline infusion. The mCPP, but not yohimbine significantly increased anxiety ratings. Both challenges produced robust ACTH, cortisol and prolactin responses. There was a significant correlation between craving and the degree of alcoholism severity. Acamprosate administration did not influence craving. Both yohimbine and mCPP challenges lead to elevated alcohol craving in a clinical population of alcoholics, and these cravings correlate with alcoholism severity. Under the experimental conditions used, alcohol cravings induced by these two stimuli are not sensitive to acamprosate at clinically used doses. PMID:21289601

  3. The prevalence and correlates of severe social withdrawal (hikikomori) in Hong Kong: A cross-sectional telephone-based survey study.

    PubMed

    Wong, Paul W C; Li, Tim M H; Chan, Melissa; Law, Y W; Chau, Michael; Cheng, Cecilia; Fu, K W; Bacon-Shone, John; Yip, Paul S F

    2015-06-01

    Severe social withdrawal behaviors among young people have been a subject of public and clinical concerns. This study aimed to explore the prevalence of social withdrawal behaviors among young people aged 12-29 years in Hong Kong. A cross-sectional telephone-based survey was conducted with 1,010 young individuals. Social withdrawal behaviors were measured with the proposed research diagnostic criteria for hikikomori and were categorized according to the (a) international proposed duration criterion (more than 6 months), (b) local proposed criterion (less than 6 months) and (c) with withdrawal behaviors but self-perceived as non-problematic. The correlates of social withdrawal among the three groups were examined using multinomial and ordinal logistic regression analyses. The prevalence rates of more than 6 months, less than 6 months and self-perceived non-problematic social withdrawal were 1.9%, 2.5% and 2.6%, respectively. In terms of the correlates, the internationally and locally defined socially withdrawn youths are similar, while the self-perceived non-problematic group is comparable to the comparison group. The study finds that the prevalence of severe social withdrawal in Hong Kong is comparable to that in Japan. Both groups with withdrawal behaviors for more or less than 6 months share similar characteristics and are related to other contemporary youth issues, for example, compensated dating and self-injury behavior. The self-perceived non-problematic group appears to be a distinct group and the withdrawal behaviors of its members may be discretionary. © The Author(s) 2014.

  4. A randomized, open-label, standard controlled, parallel group study of efficacy and safety of baclofen, and chlordiazepoxide in uncomplicated alcohol withdrawal syndrome.

    PubMed

    Girish, K; Vikram Reddy, K; Pandit, Lakshmi V; Pundarikaksha, H P; Vijendra, R; Vasundara, K; Manjunatha, R; Nagraj, Moulya; Shruthi, R

    2016-02-01

    Alcohol withdrawal syndrome (AWS) is a distressing condition, generally controlled by benzodiazepines (BZD's). Baclofen, a gamma-aminobutyric acid-B (GABAB) agonist, has also shown promising results in controlling AWS. As there are few studies comparing the efficacy and tolerability of chlordiazepoxide with baclofen, the present study was taken up. The objective of this study was to compare efficacy and tolerability of baclofen with chlordiazepoxide in uncomplicated AWS. Sixty subjects with uncomplicated AWS were randomized into two groups of 30 each, to receive baclofen (30 mg) or chlordiazepoxide (75 mg) in decremented fixed dose regime for 9 days. Clinical efficacy was assessed by Clinical Institute Withdrawal Assessment for Alcohol-Revised Scale (CIWA-Ar) and tolerability by the nature and severity of adverse events. Lorazepam was used as rescue medication. Secondary efficacy parameters were Clinical Global Impression scores, symptom-free days, and subject satisfaction as assessed by visual analog scale. This study was registered with Clinical Trial Registry-India (CTRI/2013/04/003588), also subsequently registered with WHO's ICTRP clinical trial portal. Both baclofen and chlordiazepoxide showed a consistent reduction in the total CIWA-Ar scores. However, chlordiazepoxide showed a faster and a more effective control of anxiety and agitation requiring lesser lorazepam supplementation, and also showed a better subject satisfaction compared to baclofen. Both the drugs showed good tolerability with mild self-limiting adverse events. The present study demonstrates that baclofen is not as good as chlordiazepoxide in the treatment of uncomplicated AWS. However, baclofen might be considered as an alternative. Copyright © 2016 Chang Gung University. Published by Elsevier B.V. All rights reserved.

  5. Urine methanol concentration and alcohol hangover severity.

    PubMed

    Mackus, M; Van de Loo, A J A E; Korte-Bouws, G A H; Van Neer, R H P; Wang, X; Nguyen, T T; Brookhuis, K A; Garssen, J; Verster, J C

    2017-03-01

    Congeners are substances, other than ethanol, that are produced during fermentation. Previous research found that the consumption of congener-rich drinks contributes to the severity of alcohol hangover. Methanol is such a congener that has been related to alcohol hangover. Therefore, the aim of this study was to examine the relationship between urine methanol concentration and alcohol hangover severity. N = 36 healthy social drinkers (22 females, 14 males), aged 18-30 years old, participated in a naturalistic study, comprising a hangover day and a control day (no alcohol consumed the previous day). N = 18 of them had regular hangovers (the hangover group), while the other N = 18 claimed to be hangover-immune (hangover-immune group). Overall hangover severity was assessed, and that of 23 individual hangover symptoms. Urine methanol concentrations on the hangover and control days were compared, and correlated to hangover (symptom) severity. Urine methanol concentration was significantly higher on hangover days compared to control days (p = 0.0001). No significant differences in urine methanol concentration were found between the hangover group and hangover-immune group. However, urine methanol concentration did not significantly correlate with overall hangover severity (r = -0.011, p = 0.948), nor with any of the individual hangover symptoms. These findings were observed also when analyzing the data separately for the hangover-immune group. In the hangover group, a significant correlation with urine methanol concentration was found only with vomiting (r = 0.489, p = 0.037). No significant correlation was observed between urine methanol concentration and hangover severity, nor with individual core hangover symptoms. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. 27 CFR 31.104 - Withdrawal of one or more partners.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Withdrawal of one or more partners. 31.104 Section 31.104 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... this part, the remaining partner, or partners, must register the change in control by filing an amended...

  7. 27 CFR 31.104 - Withdrawal of one or more partners.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Withdrawal of one or more partners. 31.104 Section 31.104 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... this part, the remaining partner, or partners, must register the change in control by filing an amended...

  8. Implementation of an Intensive Care Unit-Specific Alcohol Withdrawal Syndrome Management Protocol Reduces the Need for Mechanical Ventilation.

    PubMed

    Heavner, Jason J; Akgün, Kathleen M; Heavner, Mojdeh S; Eng, Claire C; Drew, Matthew; Jackson, Peter; Pritchard, David; Honiden, Shyoko

    2018-05-25

    Alcohol use disorders are prevalent and put patients at risk for developing alcohol withdrawal syndrome (AWS). Treatment of AWS with a symptom-triggered protocol standardizes management and may avoid AWS-related complications. The objective of this study was to evaluate whether implementation of an intensive care unit (ICU)-specific, symptom-triggered protocol for management of AWS was associated with improved clinical outcomes and, in particular, would reduce the risk of patients with AWS requiring mechanical ventilation. Retrospective pre-post-protocol implementation study. Thirty-six-bed, closed medical ICU (MICU) at a large, tertiary care, teaching hospital in an urban setting. A total of 233 adults admitted to the MICU with any diagnosis of alcohol use disorders based on International Classification of Diseases, Ninth Revision codes and who received at least one dose of any benzodiazepine; of these patients, 139 were in the pre-protocol era (August 2009-January 2010 and August 2010-January 2011), and 94 were in the post-protocol era (August 2012-January 2013), after implementation of the Yale Alcohol Withdrawal Protocol (YAWP) in April 2012. The YAWP pairs a modified Minnesota Detoxification Scale with an order set that includes benzodiazepine dosing regimens and suggests adjuvant therapies. AWS was the primary reason for ICU admission (107/233 patients [45.9%]) and did not significantly vary between eras (P=0.2). Of the 233 patients included, 81.1% were male and 67.0% were white, which did not significantly differ by study era. Severity of illness at MICU admission did not significantly differ between patients in the pre-protocol and post-protocol eras (median [interquartile range] Acute Physiology and Chronic Health Evaluation [APACHE] II scores of 12 [9-17] and 12.5 [7-16], respectively, p=0.4). Median lorazepam-equivalent dose per MICU day, duration of benzodiazepine infusion, and use of adjuvant therapy were not significantly different between eras. MICU

  9. Increased plasma pancreatic polypeptide in chronic alcohol abuse.

    PubMed

    Fink, R S; Adrian, T E; Margot, D H; Bloom, S R

    1983-04-01

    Post-prandial plasma gastrointestinal hormone profiles were measured in nine chronic alcoholics, one and fourteen days after complete alcohol withdrawal. Basal plasma pancreatic polypeptide concentration (PP--mean +/- SE mean) was significantly greater in alcoholics (control, 28 +/- 5 pmol/l; alcoholics, post-withdrawal day 1, 62 +/- 14 pmol/l, P less than 0.05; and post-withdrawal day 14, 89 +/- 17 pmol/1, P less than 0.005). The total integrated (TIR) PP response following a test breakfast was similarly elevated (control, 442 +/- 63 units; alcoholics, day 1, 1310 +/- 231 units, P less than 0.005; day 14,1066 +/- 66, P less than 0.005). Basal and TIR values for gastrin, gastric inhibitory peptide, insulin and glucagon were similar in alcoholics and controls. As PP has been shown to inhibit pancreatic exocrine enzyme secretion, these findings may help explain the abnormal pancreatic function seen frequently in alcoholics.

  10. Prefrontal cortex expression of chromatin modifier genes in male WSP and WSR mice changes across ethanol dependence, withdrawal, and abstinence.

    PubMed

    Hashimoto, Joel G; Gavin, David P; Wiren, Kristine M; Crabbe, John C; Guizzetti, Marina

    2017-05-01

    Alcohol-use disorder (AUD) is a relapsing disorder associated with excessive ethanol consumption. Recent studies support the involvement of epigenetic mechanisms in the development of AUD. Studies carried out so far have focused on a few specific epigenetic modifications. The goal of this project was to investigate gene expression changes of epigenetic regulators that mediate a broad array of chromatin modifications after chronic alcohol exposure, chronic alcohol exposure followed by 8 h withdrawal, and chronic alcohol exposure followed by 21 days of abstinence in Withdrawal-Resistant (WSR) and Withdrawal Seizure-Prone (WSP) selected mouse lines. We found that chronic vapor exposure to highly intoxicating levels of ethanol alters the expression of several chromatin remodeling genes measured by quantitative PCR array analyses. The identified effects were independent of selected lines, which, however, displayed baseline differences in epigenetic gene expression. We reported dysregulation in the expression of genes involved in histone acetylation, deacetylation, lysine and arginine methylation and ubiquitinationhylation during chronic ethanol exposure and withdrawal, but not after 21 days of abstinence. Ethanol-induced changes are consistent with decreased histone acetylation and with decreased deposition of the permissive ubiquitination mark H2BK120ub, associated with reduced transcription. On the other hand, ethanol-induced changes in the expression of genes involved in histone lysine methylation are consistent with increased transcription. The net result of these modifications on gene expression is likely to depend on the combination of the specific histone tail modifications present at a given time on a given promoter. Since alcohol does not modulate gene expression unidirectionally, it is not surprising that alcohol does not unidirectionally alter chromatin structure toward a closed or open state, as suggested by the results of this study. Published by Elsevier

  11. Prefrontal cortex expression of chromatin modifier genes in male WSP and WSR mice changes across ethanol dependence, withdrawal, and abstinence

    PubMed Central

    Hashimoto, Joel G.; Gavin, David P.; Wiren, Kristine M.; Crabbe, John C.; Guizzetti, Marina

    2017-01-01

    Alcohol-use disorder (AUD) is a relapsing disorder associated with excessive ethanol consumption. Recent studies support the involvement of epigenetic mechanisms in the development of AUD. Studies carried out so far have focused on a few specific epigenetic modifications. The goal of this project was to investigate gene expression changes of epigenetic regulators that mediate a broad array of chromatin modifications after chronic alcohol exposure, chronic alcohol exposure followed by 8 h withdrawal, and chronic alcohol exposure followed by 21 days of abstinence in Withdrawal-Resistant (WSR) and Withdrawal Seizure-Prone (WSP) selected mouse lines. We found that chronic vapor exposure to highly intoxicating levels of ethanol alters the expression of several chromatin remodeling genes measured by quantitative PCR array analyses. The identified effects were independent of selected lines, which, however, displayed baseline differences in epigenetic gene expression. We reported dysregulation in the expression of genes involved in histone acetylation, deacetylation, lysine and arginine methylation and ubiquitination, and in DNA methylation during chronic ethanol exposure and withdrawal, but not after 21 days of abstinence. Ethanol-induced changes are consistent with decreased histone acetylation and with decreased deposition of the permissive ubiquitination mark H2BK120ub, associated with reduced transcription. On the other hand, ethanol-induced changes in the expression of genes involved in histone lysine methylation are consistent with increased transcription. The net result of these modifications on gene expression is likely to depend on the combination of the specific histone tail modifications present at a given time on a given promoter. Since alcohol does not modulate gene expression unidirectionally, it is not surprising that alcohol does not unidirectionally alter chromatin structure toward a closed or open state, as suggested by the results of this study. PMID

  12. Mortality associated with withdrawal of life-sustaining therapy for patients with severe traumatic brain injury: a Canadian multicentre cohort study

    PubMed Central

    Turgeon, Alexis F.; Lauzier, François; Simard, Jean-François; Scales, Damon C.; Burns, Karen E.A.; Moore, Lynne; Zygun, David A.; Bernard, Francis; Meade, Maureen O.; Dung, Tran Cong; Ratnapalan, Mohana; Todd, Stephanie; Harlock, John; Fergusson, Dean A.

    2011-01-01

    Background: Severe traumatic brain injury often leads to death from withdrawal of life-sustaining therapy, although prognosis is difficult to determine. Methods: To evaluate variation in mortality following the withdrawal of life-sustaining therapy and hospital mortality in patients with critical illness and severe traumatic brain injury, we conducted a two-year multicentre retrospective cohort study in six Canadian level-one trauma centres. The effect of centre on hospital mortality and withdrawal of life-sustaining therapy was evaluated using multivariable logistic regression adjusted for baseline patient-level covariates (sex, age, pupillary reactivity and score on the Glasgow coma scale). Results: We randomly selected 720 patients with traumatic brain injury for our study. The overall hospital mortality among these patients was 228/720 (31.7%, 95% confidence interval [CI] 28.4%–35.2%) and ranged from 10.8% to 44.2% across centres (χ2 test for overall difference, p < 0.001). Most deaths (70.2% [160/228], 95% CI 63.9%–75.7%) were associated with withdrawal of life-sustaining therapy, ranging from 45.0% (18/40) to 86.8% (46/53) (χ2 test for overall difference, p < 0.001) across centres. Adjusted odd ratios (ORs) for the effect of centre on hospital mortality ranged from 0.61 to 1.55 (p < 0.001). The incidence of withdrawal of life-sustaining therapy varied by centre, with ORs ranging from 0.42 to 2.40 (p = 0.001). About one half of deaths that occurred following the withdrawal of life-sustaining therapies happened within the first three days of care. Interpretation: We observed significant variation in mortality across centres. This may be explained in part by regional variations in physician, family or community approaches to the withdrawal of life-sustaining therapy. Considering the high proportion of early deaths associated with the withdrawal of life-sustaining therapy and the limited accuracy of current prognostic indicators, caution should be used

  13. [Withdrawal of artificial nutrition and hydration in severe stroke: medical, legal and ethical considerations].

    PubMed

    Tannier, C; Crozier, S; Zuber, M; Constantinides, Y; Delezie, E; Gisquet, E; Grignoli, N; Lamy, C; Louvet, F; Pinel, J-F

    2015-02-01

    In the majority of cases, severe stroke is accompanied by difficulty in swallowing and an altered state of consciousness requiring artificial nutrition and hydration. Because of their artificial nature, nutrition and hydration are considered by law as treatment rather basic care. Withdrawal of these treatments is dictated by the refusal of unreasonable obstinacy enshrined in law and is justified by the risk of severe disability and very poor quality of life. It is usually the last among other withholding and withdrawal decisions which have already been made during the long course of the disease. Reaching a collegial consensus on a controversial decision such as artificial nutrition and hydration withdrawal is a difficult and complex process. The reluctance for such decisions is mainly due to the symbolic value of food and hydration, to the fear of "dying badly" while suffering from hunger and thirst, and to the difficult distinction between this medical act and euthanasia. The only way to overcome such reluctance is to ensure flawless accompaniment, associating sedation and appropriate comfort care with a clear explanation (with relatives but also caregivers) of the rationale and implications of this type of decision. All teams dealing with this type of situation must have thoroughly thought through the medical, legal and ethical considerations involved in making this difficult decision. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  14. Efficacy and safety of levetiracetam for outpatient alcohol detoxification.

    PubMed

    Müller, C A; Schäfer, M; Schneider, S; Heimann, H M; Hinzpeter, A; Volkmar, K; Förg, A; Heinz, A; Hein, J

    2010-07-01

    Anticonvulsant drugs are increasingly being used for alcohol detoxification in in- and outpatient settings. The aim of this study was to examine the efficacy, medical safety and mid-term outcome of levetiracetam, a drug with no marked liver toxicity, for outpatient alcohol detoxification. This was an open-label observational study. After screening eligibility for outpatient alcohol detoxification, patients were seen daily for 5 days and received levetiracetam in a flexible dosage regime between 500 and 4 000 mg/d for a maximum of 7 days. Diazepam was used as a rescue medication. The severity of alcohol withdrawal was evaluated daily using the ALCOHOL WITHDRAWAL SYNDROME SCALE (AWSS). Mid-term treatment outcome was assessed at a 6-month follow-up. A total number of 131 consecutively admitted alcohol-dependent patients received an outpatient detoxification treatment, 122 (93.1%) completed the programme successfully. The mean initial dose of levetiracetam was 1 850 mg/d. Alcohol withdrawal syndrome as indicated by the AWSS score decreased clearly over 5 days. Overall, the medication was well tolerated. There was no treatment discontinuations due to side effects of levetiracetam. No serious medical complications, especially seizures or deliria, were observed during the detoxification. At the 6-month follow-up, 57 patients (43.5%) were still abstinent. Patients with previous detoxifications had a significant higher risk for relapse (HR=1.88; p=0.016; CI 95%: 1.12-3.14) than patients without previous treatments. The findings of this study provide some evidence that levetiracetam is an efficacious and safe treatment option for outpatient alcohol detoxification. Further randomised, controlled trials including mid- and long-term follow-ups are needed to confirm these findings. Copyright Georg Thieme Verlag KG Stuttgart New York.

  15. Alprazolam use and dependence. A retrospective analysis of 30 cases of withdrawal.

    PubMed Central

    Dickinson, B; Rush, P A; Radcliffe, A B

    1990-01-01

    From 1986 to 1989, the Chemical Dependency Recovery Program at Kaiser Permanente Hospital, Fontana, California, admitted an increasing number of patients for alprazolam dependence. Severe withdrawal reactions and adverse consequences with use were reported in the literature. In this review of 30 cases of alprazolam dependence and subsequent withdrawal, there was a statistically significant increase in the number of patient hospital days, the subjective symptoms, and staff time spent with patients compared with those in alcoholic controls. Most patients with diagnosed alprazolam dependence used doses in the range recommended by the package information at the time of admission. Patients with low preadmission doses of 1 mg or less per day showed notable withdrawal symptoms. The average duration of use was 29.9 months, considerably longer than suggested effective ranges. Most patients (28) had a chemical dependence history before being placed on alprazolam therapy; 24 had a positive family history of chemical dependence; and 24 had previous or current psychiatric care. PMID:2349800

  16. Anxiety and smoking cessation outcomes in alcohol-dependent smokers.

    PubMed

    Kelly, Megan M; Grant, Christoffer; Cooper, Sharon; Cooney, Judith L

    2013-02-01

    Anxiety-related characteristics, including anxiety sensitivity and trait anxiety, are elevated in individuals with alcohol and nicotine dependence and associated with greater difficulties with quitting smoking. However, little is known about how anxiety-related characteristics are related to smoking cessation outcomes in alcohol-dependent smokers. The present study, part of a larger smoking cessation clinical trial, examined associations between anxiety sensitivity, trait anxiety, nicotine withdrawal symptoms, smoking urges, and smoking cessation outcomes in a sample of 83 alcohol-dependent smokers. Participants were enrolled in concurrent alcohol and tobacco treatment as part of a substance-abuse intensive outpatient program. Smoking cessation treatment was administered in a 3-week cognitive-behavioral format that included 8 weeks of open-label nicotine patch treatment. Information on nicotine withdrawal, smoking urges, and CO-confirmed smoking consumption rates was collected at baseline, quit date, end of behavioral treatment, and at a 1-month follow-up. Higher levels of anxiety sensitivity were associated with more smoking urges due to anticipation of negative affect relief at quit date. Higher levels of trait anxiety were associated with more smoking urges due to positive reinforcement and anticipation of relief of negative affect at quit date, as well as more severe nicotine withdrawal symptoms at the end of treatment. Levels of anxiety sensitivity and trait anxiety were not associated with Cox regression survival times to relapse. These results indicate that for alcohol-dependent smokers, levels of anxiety sensitivity and trait anxiety are important to consider in the assessment and treatment of nicotine dependence.

  17. Ethnic Differences in Presentation and Severity of Alcoholic Liver Disease

    PubMed Central

    Durbin-Johnson, Blythe; Halsted, Charles H.; Medici, Valentina

    2015-01-01

    Background The frequency of alcoholic liver disease (ALD), including alcoholic steatosis, hepatitis and cirrhosis, varies significantly by ethnicity. Methods With the goal to assess the role of ethnicity in determining the age of onset and severity of ALD and to compare the risk factors for its progression among ethnic groups, we conducted a retrospective chart review of all patients with ALD who were admitted or were followed as outpatients at University of California Davis Medical Center between 2002 and 2010. After excluding HBsAg and HIV positive subjects, we reviewed the charts of 791 ALD patients including 130 with alcoholic fatty liver, 154 with alcoholic hepatitis, and 507 with alcoholic cirrhosis. Results When controlling for all variables in the model, Hispanic patients presented at significantly 4-10 years younger ages than White/Caucasian patients, in each of the three disease severity categories and the results were confirmed after excluding HCV Ab/RNA positive subjects. There were more obese Hispanic patients than White/Caucasian patients, whereas the proportion of patients with hepatitis C was significantly greater in African/American subjects with alcoholic hepatitis and the proportion of patients with diabetes mellitus was significantly lower in White/Caucasian subjects than in Hispanic subjects with cirrhosis. The proportion of subjects with severe alcoholic hepatitis was similar in Hispanic and White/Caucasian patients, but lower in African/American subjects. Conclusion Ethnicity is a major factor affecting the age and severity of presentation of different subtypes of ALD. PMID:25702770

  18. Role of the satiety factor oleoylethanolamide in alcoholism.

    PubMed

    Bilbao, Ainhoa; Serrano, Antonia; Cippitelli, Andrea; Pavón, Francisco J; Giuffrida, Andrea; Suárez, Juan; García-Marchena, Nuria; Baixeras, Elena; Gómez de Heras, Raquel; Orio, Laura; Alén, Francisco; Ciccocioppo, Roberto; Cravatt, Benjamin F; Parsons, Loren H; Piomelli, Daniele; Rodríguez de Fonseca, Fernando

    2016-07-01

    Oleoylethanolamide (OEA) is a satiety factor that controls motivational responses to dietary fat. Here we show that alcohol administration causes the release of OEA in rodents, which in turn reduces alcohol consumption by engaging peroxisome proliferator-activated receptor-alpha (PPAR-α). This effect appears to rely on peripheral signaling mechanisms as alcohol self-administration is unaltered by intracerebral PPAR-α agonist administration, and the lesion of sensory afferent fibers (by capsaicin) abrogates the effect of systemically administered OEA on alcohol intake. Additionally, OEA is shown to block cue-induced reinstatement of alcohol-seeking behavior (an animal model of relapse) and reduce the severity of somatic withdrawal symptoms in alcohol-dependent animals. Collectively, these findings demonstrate a homeostatic role for OEA signaling in the behavioral effects of alcohol exposure and highlight OEA as a novel therapeutic target for alcohol use disorders and alcoholism. © 2015 Society for the Study of Addiction.

  19. Molecular mechanisms of synaptic remodeling in alcoholism

    PubMed Central

    Kyzar, Evan J.; Pandey, Subhash C.

    2015-01-01

    Alcohol use and alcohol addiction represent dysfunctional brain circuits resulting from neuroadaptive changes during protracted alcohol exposure and its withdrawal. Alcohol exerts a potent effect on synaptic plasticity and dendritic spine formation in specific brain regions, providing a neuroanatomical substrate for the pathophysiology of alcoholism. Epigenetics has recently emerged as a critical regulator of gene expression and synaptic plasticity-related events in the brain. Alcohol exposure and withdrawal induce changes in crucial epigenetic processes in the emotional brain circuitry (amygdala) that may be relevant to the negative affective state defined as the “dark side” of addiction. Here, we review the literature concerning synaptic plasticity and epigenetics, with a particular focus on molecular events related to dendritic remodeling during alcohol abuse and alcoholism. Targeting epigenetic processes that modulate synaptic plasticity may yield novel treatments for alcoholism. PMID:25623036

  20. Molecular mechanisms of synaptic remodeling in alcoholism.

    PubMed

    Kyzar, Evan J; Pandey, Subhash C

    2015-08-05

    Alcohol use and alcohol addiction represent dysfunctional brain circuits resulting from neuroadaptive changes during protracted alcohol exposure and its withdrawal. Alcohol exerts a potent effect on synaptic plasticity and dendritic spine formation in specific brain regions, providing a neuroanatomical substrate for the pathophysiology of alcoholism. Epigenetics has recently emerged as a critical regulator of gene expression and synaptic plasticity-related events in the brain. Alcohol exposure and withdrawal induce changes in crucial epigenetic processes in the emotional brain circuitry (amygdala) that may be relevant to the negative affective state defined as the "dark side" of addiction. Here, we review the literature concerning synaptic plasticity and epigenetics, with a particular focus on molecular events related to dendritic remodeling during alcohol abuse and alcoholism. Targeting epigenetic processes that modulate synaptic plasticity may yield novel treatments for alcoholism. Published by Elsevier Ireland Ltd.

  1. Dexmedetomidine in addition to benzodiazepine-based sedation in patients with alcohol withdrawal delirium.

    PubMed

    Tolonen, Jukka; Rossinen, Juhani; Alho, Hannu; Harjola, Veli-Pekka

    2013-12-01

    Alcohol withdrawal delirium (AWD) is often refractory to conventional medication. We report a prospective series of patients treated with α2-agonist dexmedetomidine added to conventional sedation. Eighteen patients with AWD were diagnosed by Confusion assessment method for ICU score. Treatment, complications, length of stay (LOS) in ICU and hospital were recorded. In addition, hospital and 1-year mortality were assessed. Dexmedetomidine was given for 23.9 (18.4) h [mean (SD)]. All the patients also received benzodiazepines but three patients were given haloperidole. No patient was intubated. The maximum infusion rate of dexmedetomidine was 1.5 (1.2) µg/kg/h. Time to resolution of AWD was 3.8 (1.3) days. The ICU LOS was 7.1 (2.7) days and in-hospital LOS 12.1 (4.5) days. No adverse events were observed although one patient died from acute pancreatitis. The use of dexmedetomidine in AWD seems safe but warrants further studies.

  2. Effects of Chronic Alcohol Exposure on the Modulation of Ischemia-Induced Glutamate Release via Cannabinoid Receptors in the Dorsal Hippocampus.

    PubMed

    Zheng, Lei; Wu, Xiaoda; Dong, Xiao; Ding, Xinli; Song, Cunfeng

    2015-10-01

    Chronic alcohol consumption is a critical contributing factor to ischemic stroke, as it enhances ischemia-induced glutamate release, leading to more severe excitotoxicity and brain damage. But the neural mechanisms underlying this phenomenon are poorly understood. We evaluated the effects of chronic alcohol exposure on the modulation of ischemia-induced glutamate release via CB1 and CB2 cannabinoid receptors during middle cerebral artery occlusion, using in vivo microdialysis coupled with high-performance liquid chromatography, in alcohol-naïve rats or rats after 1 or 30 days of withdrawal from chronic ethanol intake (6% v/v for 14 days). Intra-dorsal hippocampus (DH) infusions of ACEA or JWH133, selective CB1 or CB2 receptor agonists, respectively, decreased glutamate release in the DH in alcohol-naïve rats in a dose-dependent manner. Such an effect was reversed by co-infusions of SR141716A or AM630, selective CB1 or CB2 receptor antagonists, respectively. After 30 days, but not 1 day of withdrawal, ischemia induced an enhancement in glutamate release in the DH, as compared with non-alcohol-treated control group. Intra-DH infusions of JWH133, but not ACEA, inhibited ischemia-induced glutamate release in the DH after 30 days of withdrawal. Finally, 1 day of withdrawal did not alter the protein level of CB1 or CB2 receptors in the DH, as compared to non-alcohol-treated control rats. Whereas 30 days of withdrawal robustly decreased the protein level of CB1 receptors, but failed to alter the protein level of CB2 receptors, in the DH, as compared to non-alcohol-treated control rats. Together, these findings suggest that loss of expression/function of CB1 receptors, but not CB2 receptors in the DH, is correlated with the enhancement of ischemia-induced glutamate release after prolonged alcohol withdrawal. Copyright © 2015 by the Research Society on Alcoholism.

  3. Family Based Prevention of Alcohol and Risky Sex for Older Teens

    ClinicalTrials.gov

    2018-05-08

    Alcohol Drinking; Alcohol Intoxication; Alcohol Poison; Alcohol-Related Disorders; Alcohol Impairment; Alcohol Withdrawal; Alcohol Abstinence; Alcohol; Harmful Use; Sex Behavior; Sexual Aggression; Sexual Harassment; Relation, Interpersonal

  4. Predicting Post-Treatment-Initiation Alcohol Use among Patients with Severe Mental Illness and Alcohol Use Disorders

    ERIC Educational Resources Information Center

    Bradizza, Clara M.; Maisto, Stephen A.; Vincent, Paula C.; Stasiewicz, Paul R.; Connors, Gerard J.; Mercer, Nicole D.

    2009-01-01

    Few investigators studying alcohol abuse among individuals with a severe mental illness (SMI) have examined predictors of posttreatment alcohol outcomes. In the present study, a multivariate approach based on a theoretical model was used to study the relationship between psychosocial factors and post-treatment-initiation alcohol use. Predictors of…

  5. [Correction of hydrodynamic disorders in severe alcohol poisoning in adolescent].

    PubMed

    Simakov, A A; Ostreĭkov, I F; Sukhodolova, G N; Dolginov, D M

    2014-01-01

    To improve the results of treatment of children with severe alcohol poisoning as a result of investigation of water sectors of the body. The study included 54 patients aged from 13 to 15 years with a diagnosis of acute severe alcohol poisoning. All patients were divided into three groups. At the initial examination was determined the concentration of alcohol in saliva using Express-test "Alkoskan." Bioimpedance analysis was performed; water sectors of the body were investigated by analyzer of the balance of water sectors ABC-01 "Medass." The study was conducted at the time of admission, after 12, 24 and 48 hours. In severe alcohol poisoning at the time of admission, it was revealed a reduction of the fluid in all studied sectors. The most effective compensation of liquid was observed in groups, where was used combination therapy included intravenous fluids based 4.0 ml/kg/hour. The treatment of severe alcohol poisoning should include fluid resuscitation about 4 ml/kg/hour. This capacity of medical care give the ability to correct adequately the water-sectoral disturbances already in the first 12 hours of hospitalization, and the inclusion to the basic therapy reamberine can contribute more effective replenishment of water sectors.

  6. Differences in Severity and Outcomes Between Hypertriglyceridemia and Alcohol-Induced Pancreatitis

    PubMed Central

    Goyal, Hemant; Smith, Betsy; Bayer, Chelsey; Rutherford, Carla; Shelnut, Danielle

    2016-01-01

    Background: Alcohol and hypertriglyceridemia (HTG) are among the most common causes of acute pancreatitis (AP) after gallstones. However, differences in severity at the time of presentation and outcomes have not been well-studied. Objective: The aim of this study is to assess the differences between severity at presentation and outcomes of AP of hypertriglyceridemic and alcoholic origins. Materials and Methods: A retrospective review of 177 patients who were discharged with diagnosis of AP was performed. Severity at presentation was identified by the presence of systemic inflammatory response syndrome, bedside index for severity in AP (BISAP) score, and Balthazar index. Outcomes were measured by the length of stay, intensive care unit care, surgical intervention, and mortality. Results: We found 147 patients with alcoholic pancreatitis and 30 patients with hypertriglyceridemic pancreatitis. A larger percentage of hypertriglyceridemic pancreatitis patients (23.33%) had a BISAP score of ≥2 compared to the alcoholic group (12.24%). Only 32.65% of the patients with alcoholic pancreatitis but 60% of the patients with hypertriglyceridemic pancreatitis had the presence of systemic inflammatory response syndrome (SIRS) at admission (P = 0.0067). There were 73.34% hypertriglyceridemic pancreatits patients and only 40.28% alcoholic pancreatitis patients with Balthazar index C or greater, suggesting a higher disease burden at admission for hypertriglyceridemic pancreatitis patients (P = 0.0047). There was a statistically significant difference in the relative number of hypertriglyceridemic and alcoholic pancreatitis patients receiving intensive care (P = 0.00030) and in receiving surgical interventions related to pancreatitis (P = 0.016). Conclusion: Our study found that patients with hypertriglyceridemic pancreatitis have a greater severity of disease and they experience less favorable outcomes than patients with alcoholic pancreatitis. PMID:27042605

  7. Prenatal and adult androgen activities in alcohol dependence.

    PubMed

    Lenz, B; Mühle, C; Braun, B; Weinland, C; Bouna-Pyrrou, P; Behrens, J; Kubis, S; Mikolaiczik, K; Muschler, M-R; Saigali, S; Sibach, M; Tanovska, P; Huber, S E; Hoppe, U; Eichler, A; Heinrich, H; Moll, G H; Engel, A; Goecke, T W; Beckmann, M W; Fasching, P A; Müller, C P; Kornhuber, J

    2017-07-01

    Alcohol dependence is more prevalent in men than in women. The evidence for how prenatal and adult androgens influence alcohol dependence is limited. We investigated the effects of prenatal and adult androgen activity on alcohol dependence. Moreover, we studied how the behaviours of pregnant women affect their children's prenatal androgen load. We quantified prenatal androgen markers (e.g., second-to-fourth finger length ratio [2D : 4D]) and blood androgens in 200 early-abstinent alcohol-dependent in-patients and 240 controls (2013-2015, including a 12-month follow-up). We also surveyed 134 women during pregnancy (2005-2007) and measured the 2D : 4D of their children (2013-2016). The prenatal androgen loads were higher in the male alcohol-dependent patients compared to the controls (lower 2D : 4D, P = 0.004) and correlated positively with the patients' liver transaminase activities (P < 0.001) and alcohol withdrawal severity (P = 0.019). Higher prenatal androgen loads and increasing androgen levels during withdrawal predicted earlier and more frequent 12-month hospital readmission in alcohol-dependent patients (P < 0.005). Moreover, stress levels (P = 0.002), alcohol (P = 0.010) and tobacco consumption (P = 0.017), and lifetime stressors (P = 0.019) of women during pregnancy related positively to their children's prenatal androgen loads (lower 2D : 4D). Androgen activities in alcohol-dependent patients and behaviours of pregnant women represent novel preventive and therapeutic targets of alcohol dependence. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Effects of Acute Withdrawal on Ethanol-Induced Conditioned Place Preference in DBA/2J mice

    PubMed Central

    Dreumont, Sarah E.; Cunningham, Christopher L.

    2013-01-01

    Rationale Re-exposure to ethanol during acute withdrawal might facilitate the transition to alcoholism by enhancing the rewarding effect of ethanol. Objective The conditioned place preference (CPP) procedure was used to test whether ethanol reward is enhanced during acute withdrawal. Methods DBA/2J mice were exposed to an unbiased one-compartment CPP procedure. Ethanol (0.75, 1.0 or 1.5 g/kg IP) was paired with a distinctive floor cue (CS+), whereas saline was paired with a different floor cue (CS−). The Withdrawal (W) group received CS+ trials during acute withdrawal produced by a large dose of ethanol (4 g/kg) given 8 h before each trial. The No Withdrawal (NW) group did not experience acute withdrawal during conditioning trials, but was matched for acute withdrawal experience. Floor preference was tested in the absence of ethanol or acute withdrawal. Results All groups eventually showed a dose-dependent preference for the ethanol-paired cue, but development of CPP was generally more rapid and stable in the W groups than in the NW groups. Acute withdrawal suppressed the normal activating effect of ethanol during CS+ trials, but there were no group differences in test activity. Conclusions Acute withdrawal enhanced ethanol’s rewarding effect as indexed by CPP. Since this effect depended on ethanol exposure during acute withdrawal, the enhancement of ethanol reward was likely mediated by the alleviation of acute withdrawal, i.e., negative reinforcement. Enhancement of ethanol reward during acute withdrawal may be a key component in the shift from episodic to chronic ethanol consumption that characterizes alcoholism. PMID:24096534

  9. Chronic ethanol intake induces partial microglial activation that is not reversed by long-term ethanol withdrawal in the rat hippocampal formation.

    PubMed

    Cruz, Catarina; Meireles, Manuela; Silva, Susana M

    2017-05-01

    Neuroinflammation has been implicated in the pathogenesis of several disorders. Activation of microglia leads to the release of pro-inflammatory mediators and microglial-mediated neuroinflammation has been proposed as one of the alcohol-induced neuropathological mechanisms. The present study aimed to examine the effect of chronic ethanol exposure and long-term withdrawal on microglial activation and neuroinflammation in the hippocampal formation. Male rats were submitted to 6 months of ethanol treatment followed by a 2-month withdrawal period. Stereological methods were applied to estimate the total number of microglia and activated microglia detected by CD11b immunohistochemistry in the hippocampal formation. The expression levels of the pro-inflammatory cytokines TNF-α, COX-2 and IL-15 were measured by qRT-PCR. Alcohol consumption was associated with an increase in the total number of activated microglia but morphological assessment indicated that microglia did not exhibit a full activation phenotype. These data were supported by functional evidence since chronic alcohol consumption produced no changes in the expression of TNF-α or COX-2. The levels of IL-15 a cytokine whose expression is increased upon activation of both astrocytes and microglia, was induced by chronic alcohol treatment. Importantly, the partial activation of microglia induced by ethanol was not reversed by long-term withdrawal. This study suggests that chronic alcohol exposure induces a microglial phenotype consistent with partial activation without significant increase in classical cytokine markers of neuroinflammation in the hippocampal formation. Furthermore, long-term cessation of alcohol intake is not sufficient to alter the microglial partial activation phenotype induced by ethanol. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Linkage analyses of cannabis dependence, craving, and withdrawal in the San Francisco family study.

    PubMed

    Ehlers, Cindy L; Gizer, Ian R; Vieten, Cassandra; Wilhelmsen, Kirk C

    2010-04-05

    Cannabis is the most widely used illicit drug in the United States. There is ample evidence that cannabis use has a heritable component, yet the genes underlying cannabis use disorders are yet to be completely identified. This study's aims were to map susceptibility loci for cannabis use and dependence and two narrower cannabis-related phenotypes of "craving" and "withdrawal" using a family study design. Participants were 2,524 adults participating in the University of California San Francisco (UCSF) Family Alcoholism Study. DSM-IV diagnoses of cannabis dependence, as well as indices of cannabis craving and withdrawal, were obtained using a modified version of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). Genotypes were determined for a panel of 791 microsatellite polymorphisms. Multipoint variance component LOD scores were obtained using SOLAR. Genome-wide significance for linkage (LOD > 3.0) was not found for the DSM-IV cannabis dependence diagnosis; however, linkage analyses of cannabis "craving" and the cannabis withdrawal symptom of "nervous, tense, restless, or irritable" revealed five sites with LOD scores over 3.0 on chromosomes 1, 3, 6, 7, and 9. These results identify new regions of the genome associated with cannabis use phenotypes as well as corroborate the importance of several chromosome regions highlighted in previous linkage analyses for other substance dependence phenotypes.

  11. Differences in the subjective and motivational properties of alcohol across alcohol use severity: application of a novel translational human laboratory paradigm.

    PubMed

    Bujarski, Spencer; Jentsch, J David; Roche, Daniel J O; Ramchandani, Vijay A; Miotto, Karen; Ray, Lara A

    2018-05-08

    The Allostatic Model proposes that Alcohol Use Disorder (AUD) is associated with a transition in the motivational structure of alcohol drinking: from positive reinforcement in early-stage drinking to negative reinforcement in late-stage dependence. However, direct empirical support for this preclinical model from human experiments is limited. This study tests predictions derived from the Allostatic Model in humans. Specifically, this study tested whether alcohol use severity (1) independently predicts subjective responses to alcohol (SR; comprised of stimulation/hedonia, negative affect, sedation and craving domains), and alcohol self-administration and 2) moderates associations between domains of SR and alcohol self-administration. Heavy drinking participants ranging in severity of alcohol use and problems (N = 67) completed an intravenous alcohol administration paradigm combining an alcohol challenge (target BrAC = 60 mg%), with progressive ratio self-administration. Alcohol use severity was associated with greater baseline negative affect, sedation, and craving but did not predict changes in any SR domain during the alcohol challenge. Alcohol use severity also predicted greater self-administration. Craving during the alcohol challenge strongly predicted self-administration and sedation predicted lower self-administration. Neither stimulation, nor negative affect predicted self-administration. This study represents a novel approach to translating preclinical neuroscientific theories to the human laboratory. As expected, craving predicted self-administration and sedation was protective. Contrary to the predictions of the Allostatic Model, however, these results were inconsistent with a transition from positively to negatively reinforced alcohol consumption in severe AUD. Future studies that assess negative reinforcement in the context of an acute stressor are warranted.

  12. Chronic voluntary alcohol consumption results in tolerance to sedative/hypnotic and hypothermic effects of alcohol in hybrid mice

    PubMed Central

    Ozburn, Angela Renee; Harris, R. Adron; Blednov, Yuri A.

    2013-01-01

    The continuous two bottle choice test is the most common measure of alcohol consumption but there is remarkably little information about the development of tolerance or dependence with this procedure. We showed that C57BL/6JxFVB/NJ and FVB/NJxC57BL/6J F1 hybrid mice demonstrate greater preference for and consumption of alcohol than either parental strain. In order to test the ability of this genetic model of high alcohol consumption to produce neuroadaptation, we examined development of alcohol tolerance and dependence after chronic self-administration using a continuous access two-bottle choice paradigm. Ethanol-experienced mice stably consumed about 16–18 g/kg/day of ethanol. Ethanol-induced withdrawal severity was assessed (after 59 days of drinking) by scoring handling-induced convulsions; withdrawal severity was minimal and did not differ between ethanol-experienced and -naïve mice. After 71 days of drinking, the rate of ethanol clearance was similar for ethanol-experienced and -naïve mice. After 77 days of drinking, ethanol-induced loss of righting reflex (LORR) was tested daily for 5 days. Ethanol-experienced mice had a shorter duration of LORR. For both ethanol-experienced and -naïve mice, blood ethanol concentrations taken at gain of righting reflex were greater on day 5 than on day 1, indicative of tolerance. After 98 days of drinking, ethanol-induced hypothermia was assessed daily for 3 days. Both ethanol-experienced and –naïve mice developed rapid and chronic tolerance to ethanol-induced hypothermia, with significant group differences on the first day of testing. In summary, chronic, high levels of alcohol consumption in F1 hybrid mice produced rapid and chronic tolerance to both the sedative/hypnotic and hypothermic effects of ethanol; additionally, a small degree of metabolic tolerance developed. The development of tolerance supports the validity of using this model of high alcohol consumption in genetic studies of alcoholism. PMID:23313769

  13. Fear of driving license withdrawal in patients with insulin-treated diabetes mellitus negatively influences their decision to report severe hypoglycemic events to physicians.

    PubMed

    Brož, Jan; Brabec, Marek; Janíčková Žďárská, Denisa; Fedáková, Zuzana; Hoskovcová, Lucie; You, Jee Young; Doničová, Viera; Hlaďo, Petr; Rahelić, Dario; Kvapil, Milan; Polák, Jan

    2015-01-01

    Under current European Union legislation, two severe hypoglycemic events within 12 months is grounds for driving license withdrawal. The aim of the study reported here was to determine whether fear of such a withdrawal could lead to patients concealing severe hypoglycemia from physicians, which could negatively impact further treatment decisions. A total of 663 patients with insulin-treated diabetes were anonymously surveyed about whether they would conceal severe hypoglycemic events from their physicians, if revealing them could result in driving license withdrawal. This investigation utilized an adapted and expanded questionnaire by Graveling et al. Of all diabetic patients surveyed, 26.17% would most likely not report hypoglycemia, and 25.86% were undecided. In a group of patients with type 1 diabetes, 31.83% would likely not report hypoglycemic events, and 25.06% were undecided. The patients least likely to report severe hypoglycemic events were those who indicated that vehicles were partly essential for work, and who also had more than two hypoglycemic events monthly. A considerable percentage of diabetic patients would likely conceal severe hypoglycemic events from their physicians due to fear of driving license withdrawal. Patient failure to report severe hypoglycemic events can potentially lead to physicians being misinformed regarding the patient's condition, which could lead to inadequate monitoring and treatment.

  14. Examining the Associations among Severity of Injunctive Drinking Norms, Alcohol Consumption, and Alcohol-Related Negative Consequences: The Moderating Roles of Alcohol Consumption and Identity

    PubMed Central

    Lewis, Melissa A.; Neighbors, Clayton; Geisner, Irene Markman; Lee, Christine M.; Kilmer, Jason R.; Atkins, David C.

    2009-01-01

    The present study examined a range of injunctive norms for alcohol use and related consequences from less severe behaviors (e.g., drinking with friends) to more severe behaviors (e.g., drinking enough alcohol to pass out), and their relationship with alcohol consumption and alcohol-related negative consequences among college students. In addition, this research aimed to determine if these relationships between injunctive norms and consequences were moderated by alcohol consumption and level of identification with the typical same-sex college student. A random sample (N = 1,002) of undergraduates (56.9% female) completed a Web–based survey that was comprised of measures of drinking behavior, perceived approval of drinking behaviors that ranged in severity (i.e., injunctive norms), and level of identification with the typical same-sex college student. Results suggest that the association between negative consequences and injunctive drinking norms depend on one's own drinking behavior, identification with other students, and the severity of the alcohol use and related consequences for which injunctive norms are assessed. Findings are discussed in terms of false consensus and false uniqueness effects, and deviance regulation perspectives. Implications for preventative interventions are discussed. PMID:20565144

  15. Determinants of improvement in quality of life of alcohol-dependent patients during an inpatient withdrawal programme

    PubMed Central

    Lahmek, Pierre; Berlin, Ivan; Michel, Laurent; Berghout, Chafia; Meunier, Nadine; Aubin, Henri-Jean

    2009-01-01

    Background: To investigate the improvement in quality of life (QoL) of alcohol-dependent patients during a 3-week inpatient withdrawal programme, and to identify the sociodemographic, clinical and alcohol-related variables associated with baseline QoL on admission and with improvement of QoL during residential treatment. Methods: This prospective, observational study included 414 alcohol-dependent patients, hospitalised for a period of 3 weeks. QoL was measured on admission and at discharge using the French version of the Medical Outcome Study SF-36. The mean scores for each dimension and for the Physical and Mental Component Summary scores were calculated. Results: The mean scores per dimension and the mean Physical and Mental Component Summary scores were significantly lower on admission than at discharge; the lowest scores being observed for social functioning and role limitations due to emotional problems. At discharge, the mean scores per dimension were similar to those observed in the French general population. Female gender, age >45 years, living alone, working as a labourer or employee, somatic comorbidity, and the existence of at least five criteria for alcohol dependence according to the DSM-IV classification were associated with a low Physical Component Summary score on admission; psychiatric comorbidity, the presence of at least five DSM-IV dependence criteria, smoking and suicidality were associated with a low Mental Component Summary score on admission. The increase in Physical and Mental Component Summary scores during hospitalisation was more marked when the initial scores were low. Apart from the initial score, the greatest improvement in Physical Component Summary score was seen in patients with a high alcohol intake and in those without a somatic comorbidity; the increase in Mental Component Summary score was greatest in patients without psychotic symptoms and in those who abused or were dependent on illegal drugs. Conclusion: QoL improvement

  16. Determinants of improvement in quality of life of alcohol-dependent patients during an inpatient withdrawal programme.

    PubMed

    Lahmek, Pierre; Berlin, Ivan; Michel, Laurent; Berghout, Chafia; Meunier, Nadine; Aubin, Henri-Jean

    2009-05-18

    To investigate the improvement in quality of life (QoL) of alcohol-dependent patients during a 3-week inpatient withdrawal programme, and to identify the sociodemographic, clinical and alcohol-related variables associated with baseline QoL on admission and with improvement of QoL during residential treatment. This prospective, observational study included 414 alcohol-dependent patients, hospitalised for a period of 3 weeks. QoL was measured on admission and at discharge using the French version of the Medical Outcome Study SF-36. The mean scores for each dimension and for the Physical and Mental Component Summary scores were calculated. The mean scores per dimension and the mean Physical and Mental Component Summary scores were significantly lower on admission than at discharge; the lowest scores being observed for social functioning and role limitations due to emotional problems. At discharge, the mean scores per dimension were similar to those observed in the French general population. Female gender, age > 45 years, living alone, working as a labourer or employee, somatic comorbidity, and the existence of at least five criteria for alcohol dependence according to the DSM-IV classification were associated with a low Physical Component Summary score on admission; psychiatric comorbidity, the presence of at least five DSM-IV dependence criteria, smoking and suicidality were associated with a low Mental Component Summary score on admission. The increase in Physical and Mental Component Summary scores during hospitalisation was more marked when the initial scores were low. Apart from the initial score, the greatest improvement in Physical Component Summary score was seen in patients with a high alcohol intake and in those without a somatic comorbidity; the increase in Mental Component Summary score was greatest in patients without psychotic symptoms and in those who abused or were dependent on illegal drugs. QoL improvement after a residential treatment was related to

  17. Alcohol Alert: Genetics of Alcoholism

    MedlinePlus

    ... Reilly, M.T.; et al. Mpdz is a quantitative trait gene for drug withdrawal seizures. Nature Neuroscience 7(7):699–700, 2014. PMID: 15208631 . 12 Hurley, T.D., and Edenberg, H.J. Genes encoding enzymes involved in ethanol metabolism. Alcohol Research & Health 34:339–344, 2012 13 Yokoyama, A.; ...

  18. [Causes of the people death from drunkenness and alcoholism].

    PubMed

    Erokhin, Iu A; Paukov, V S; Kirillov, Iu A

    2012-01-01

    We analyzed causes of 1008 people death, who abused by alcohol. Among them 2 groups were separated out: people died due to drunkenness and due to alcoholism. The structure of the death was similar in the both groups, however depended on alcoholism stages. The major cause of the death in group of drunkenness people was acute heart insufficiency, less commonly--lung pathology, and very rarely--brain vessels pathology and liver cirrhosis. In group of people, who died due to alcoholism, lung pathology was the major cause of these deaths, acute heart insufficiency was occurred less commonly, and very rare brain pathology because of delirium tremens or alcohol withdrawal syndrome, as so liver cirrhosis with complications. Hemorrhagic pancreonecrosis after alcoholic excess was found out in both groups, but it was more often in people, who died due to drunkenness. Obtained results show importance of chronic alcoholism identification as a disease with several stages including drunkenness and alcoholism.

  19. [Alcoholic ketoacidosis and reversible neurological complications due to hypophosphataemia].

    PubMed

    Fernández López, Ma T; García Bargo, Ma D; Rivero Luis, Ma T; Álvarez Vázquez, P; Saenz Fernández, C A; Mato Mato, J A

    2012-01-01

    A 57-year-old man with chronic alcoholism was admitted to our hospital due to disturbance of consciousness and polyradiculitis. Laboratory examination revealed metabolic acidosis, hypokalemia and hypophosphataemia. Alcoholic ketoacidosis is a common disorder in alcoholic patients. All patients present with a history of heavy alcohol misuse, preceding a bout of particularly excesive intake, which had been terminated by nausea, vomiting and abdominal pain. The most important laboratory results are: normal or low glucose level, metabolic acidosis with a raised anion GAP, low or absent blood alcohol level and urinary ketones. The greatest threats to patients are: hypovolemia, hypokaliemia, hypoglucemia and acidosis. Alcohol abuse may result in a wide range of electrolyte and acid-base disorders including hypophosphataemia, hypomagnesemia, hypocalcemia, hypokalemia, metabolic acidosis and respiratory alkalosis. Disturbance of consciousness in alcoholic patients is observed in several disorders, such drunkenness, Wernicke encephalopathy, alcohol withdrawal syndrome, central pontine myelinolysis, hepatic encephalopathy, hypoglucemia and electrolyte disorders.

  20. 27 CFR 28.28 - Withdrawal of wine and distilled spirits from customs bonded warehouses.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Withdrawal of wine and... Miscellaneous Provisions Customs Bonded Warehouses § 28.28 Withdrawal of wine and distilled spirits from customs bonded warehouses. Wine and bottled distilled spirits entered into customs bonded warehouses as provided...

  1. Obsessive-compulsive symptoms among alcoholics in outpatient treatment: Prevalence, severity and correlates.

    PubMed

    Campos, Luana Moraes; Yoshimi, Nicoli Tamie; Simão, Maria Odete; Torresan, Ricardo Cezar; Torres, Albina Rodrigues

    2015-09-30

    The literature on symptoms of obsessive-compulsive disorder (OCD) in alcoholic patients is scarce and such symptoms can go unnoticed, worsening the prognosis of alcoholism. The objectives were to estimate the prevalence and severity of obsessive-compulsive symptoms in alcoholics undergoing outpatient treatment and to assess sociodemographic and clinical correlates, including suicidal behaviors. The instruments used in this cross-sectional study were the Obsessive-Compulsive Inventory - Revised (OCI-R), the Short Alcohol Dependence Data and the Beck Depression Inventory. After descriptive analyses, bivariate analyses between the categorical ("probable OCD": OCI-R≥27) and dimensional (OCI-R total and subscales scores) outcomes and all explanatory variables were conducted. Eleven (20.4%) of the 54 alcoholic patients (37 men and 17 women) presented "probable OCD", which was associated with lower income, more severe dependence, depression, lifetime suicidal thoughts and plans and suicide attempts. OCI-R severity (mean 16.0) was associated with the same predictors and with psychiatric hospitalization. Suicidal behaviors were mainly associated with the Obsession, Hoarding and Washing subscales. It is essential to investigate and treat OCD symptoms in alcoholics, as they are associated with greater severity of dependence, depression and suicidal behaviors. Longitudinal studies are required to assess the impact of OCD treatment on the clinical course of alcoholism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Persistent Adaptation by Chronic Alcohol is Facilitated by Neuroimmune Activation Linked to Stress and CRF

    PubMed Central

    Breese, George R.; Knapp, Darin J.

    2016-01-01

    This review updates the conceptual basis for the association of alcohol abuse with an insidious adaptation that facilitates negative affect during withdrawal from chronic intermittent alcohol (CIA) exposure – a change that later supports sensitization of stress-induced anxiety following alcohol abstinence. The finding that a CRF1-receptor antagonist (CRF1RA) minimized CIA withdrawal-induced negative affect supported an association of alcohol withdrawal with a stress mechanism. The finding that repeated stresses or multiple CRF injections into selected brain sites prior to a single 5-day chronic alcohol (CA) exposure induced anxiety during withdrawal provided critical support for a linkage of CIA withdrawal with stress. The determination that CRF1RA injection into positive CRF-sensitive brain sites prevented CIA withdrawal-induced anxiety provided support that neural path integration maintains the persistent CIA adaptation. Based upon reports that stress increases neuroimmune function, an effort was undertaken to test whether cytokines would support the adaptation induced by stress/CA exposure. Twenty-four hours after withdrawal from CIA, cytokine mRNAs were found to be increased in cortex as well as other sites in brain. Further, repeated cytokine injections into previously identified brain sites substituted for stress and CRF induction of anxiety during CA withdrawal. Discovery that a CRF1RA prevented the brain cytokine mRNA increase induced by CA withdrawal provided critical evidence for CRF involvement in this neuroimmune induction after CA withdrawal. However, the CRF1RA did not block the stress increase in cytokine mRNA increases in controls. The latter data supported the hypothesis that distinct mechanisms linked to stress and CA withdrawal can support common neuroimmune functions within a brain site. As evidence evolves concerning neural involvement in brain neuroimmune function, a better understanding of the progressive adaptation associated with CIA

  3. Does Reducing Withdrawal Severity Mediate Nicotine Patch Efficacy? A Randomized Clinical Trial

    ERIC Educational Resources Information Center

    Ferguson, Stuart G.; Shiffman, Saul; Gwaltney, Chad J.

    2006-01-01

    Nicotine replacement therapy (NRT) repeatedly has been shown to improve smoking treatment outcome. The major mechanism posited for this improvement in outcome is that NRT reduces nicotine craving and withdrawal. The authors tested this hypothesized mechanism of action using real-time data on craving and withdrawal, collected by ecological…

  4. The Addiction Severity Index: reliability and validity in a Dutch alcoholic population.

    PubMed

    DeJong, C A; Willems, J C; Schippers, G M; Hendriks, V M

    1995-04-01

    The Addiction Severity Index (ASI) was evaluated for its psychometric qualities in a Dutch alcoholic population admitted to an addiction treatment center in The Netherlands. Its factorial structure in this population was found to be consistent with the established six factor structure of the ASI. Reliability analysis revealed that the homogeneity of the subscales was acceptable with the exception of the Alcohol Scale. The six subscales were not highly intercorrelated. The results of this study indicate that the ASI is a useful instrument for the assessment of several problems associated with alcoholism. However, the Alcohol Scale appears to be limited as a diagnostic and research instrument in the field of inpatient treatment of alcohol dependence in The Netherlands.

  5. Protracted ethanol withdrawal in rats: Tolerance to the anxiolytic effects of diazepam and pentobarbital but not phenobarbital

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lai, H.; Prather, P.L.

    1990-02-26

    Anxiety is a common symptom during ethanol withdrawal contributing to its continuous abuse and alcoholism. Ethanol withdrawal in rats produces an interoceptive discriminative stimulus (IDS) similar to that produced by the anxiogenic drug pentylenetetrazol (PTZ). This stimulus peaks at 12 hours after last dose of ethanol and thereafter the IDS is detected for several days (protracted withdrawal) by sensitization to a probe drug. previously, the authors have shown that during the protracted withdrawal, the IDS is enhanced by GABA receptor antagonists suggesting alteration of brain GABA systems. This report provides further evidence that chronic ethanol alters GABAergic systems. Rats weremore » trained to discriminate PTZ (20 mg/kg, ip) from saline. Diazepam, pentobarbital and phenobarbital blocked the PTZ-IDS dose dependently. Ethanol, 4.5% w/v, was then given in a nutritionally complete diet for a week. On termination of the ethanol diet, rats exhibited signs and symptoms of withdrawal which returned to baseline within 3 days. During the protracted withdrawal period, the authors then redetermined the blockade of the PTZ-IDS. Significant tolerance was observed to the effectiveness of diazepam and pentobarbital, but not to phenobarbital. Since diazepam and pentobarbital produce significantly more enhancement of GABAergic activity than does phenobarbital, these data further suggest alteration of brain GABAergic systems during protracted withdrawal from ethanol.« less

  6. Modulation of Ethanol Withdrawal–Induced Anxiety-Like Behavior During Later Withdrawals by Treatment of Early Withdrawals With Benzodiazepine/γ-Aminobutyric Acid Ligands

    PubMed Central

    Knapp, Darin J.; Overstreet, David H.; Breese, George R.

    2010-01-01

    Background Anxiety states, including those arising during acute or protracted withdrawal periods, may be precipitating factors in alcoholic relapse. Given the cyclical nature of ethanol withdrawal associated with repeated cycles of ethanol intake and abstinence in a pattern that often spans years, meaningful attempts to model ethanol withdrawal–associated anxiety should incorporate cycled ethanol treatments. The studies reported herein examined the effects of γ-aminobutyric acid–modulating drugs on social interaction behavior—an established model of anxiety—in rats exposed to repeated cycles of ethanol treatment and withdrawal. Methods Rats were exposed to 8 to 12 g/kg/day ethanol during three 7-day dietary cycles (5 days on ethanol diet followed by 2 days on control diet). Ethanol was administered either at hour 4 of withdrawal after cessation of each of the first 2 ethanol cycles or during the final withdrawal only. In other groups, the early withdrawals were treated with alphaxalone, diazepam, PK11159, or flumazenil to block anxiety-like behavior during an untreated later (third) withdrawal. The benzodiazepine inverse agonist DMCM (methyl–6, 7–dymerhoxy–4–ethyl–beta–carboline–3–carboxylate) was also given repeatedly to determine whether it would sensitize anxiety-like behavior during a future withdrawal. Finally, the effects of all drugs on deficits in locomotor behavior were assessed. Results Pretreatment of earlier withdrawals with alphaxalone, diazepam, ethanol, or flumazenil reduced social interaction deficits during a later withdrawal, but pretreatment with PK11195 did not. In contrast, DMCM administered in lieu of early withdrawals increased social interaction deficits during an untreated later withdrawal. Locomotor deficits were significantly reversed only by the acute ethanol and diazepam treatment during the final withdrawal. Conclusions Single-dose administration of drugs that enhance or diminish activity at benzodiazepine

  7. Daily home-based spirometry during withdrawal of inhaled corticosteroid in severe to very severe chronic obstructive pulmonary disease

    PubMed Central

    Rodriguez-Roisin, Roberto; Tetzlaff, Kay; Watz, Henrik; Wouters, Emiel FM; Disse, Bernd; Finnigan, Helen; Magnussen, Helgo; Calverley, Peter MA

    2016-01-01

    The WISDOM study (NCT00975195) reported a change in lung function following withdrawal of fluticasone propionate in patients with severe to very severe COPD treated with tiotropium and salmeterol. However, little is known about the validity of home-based spirometry measurements of lung function in COPD. Therefore, as part of this study, following suitable training, patients recorded daily home-based spirometry measurements in addition to undergoing periodic in-clinic spirometric testing throughout the study duration. We subsequently determined the validity of home-based spirometry for detecting changes in lung function by comparing in-clinic and home-based forced expiratory volume in 1 second in patients who underwent stepwise fluticasone propionate withdrawal over 12 weeks versus patients remaining on fluticasone propionate for 52 weeks. Bland–Altman analysis of these data confirmed good agreement between in-clinic and home-based measurements, both across all visits and at the individual visits at study weeks 6, 12, 18, and 52. There was a measurable difference between the forced expiratory volume in 1 second values recorded at home and in the clinic (mean difference of −0.05 L), which may be due to suboptimal patient effort in performing unsupervised recordings. However, this difference remained consistent over time. Overall, these data demonstrate that home-based and in-clinic spirometric measurements were equally valid and reliable for assessing lung function in patients with COPD, and suggest that home-based spirometry may be a useful tool to facilitate analysis of changes in lung function on a day-to-day basis. PMID:27578972

  8. Animal models of alcoholism: neurobiology of high alcohol-drinking behavior in rodents.

    PubMed

    McBride, W J; Li, T K

    1998-01-01

    This review discusses efforts to develop rodent models for the study of neurobiological mechanisms underlying chronic alcohol drinking, alcoholism, and abnormal alcohol-seeking behavior. Selective breeding has produced stable lines of rats that reliably exhibit high and (for comparison purposes) low voluntary alcohol consumption. In addition, animal models of chronic ethanol self-administration have been developed in rodents, who do not have a genetic predisposition for high alcohol-seeking behavior, to explore environmental influences in ethanol drinking and the effects of physical dependence on alcohol self-administration. The selectively bred high-preference animals reliably self-administer ethanol by free-choice drinking and operantly respond for oral ethanol in amounts that produce pharmacologically meaningful blood alcohol concentrations (50 to 200 mg% and higher). In addition, the alcohol-preferring rats will self-administer ethanol by intragastric infusion. With chronic free-choice drinking, the high alcohol-preferring rats develop tolerance to the high-dose effects of ethanol and show signs of physical dependence after the withdrawal of alcohol. Compared with nonpreferring animals, the alcohol-preferring rats are less sensitive to the sedative-hypnotic effects of ethanol and develop tolerance more quickly to high-dose ethanol. Nonselected common stock rats can be trained to chronically self-administer ethanol following its initial presentation in a palatable sucrose or saccharin solution, and the gradual replacement of the sucrose or saccharin with ethanol (the sucrose/saccharin-fade technique). Moreover, rats that are trained in this manner and then made dependent by ethanol-vapor inhalation or liquid diet increase their ethanol self-administration during the withdrawal period. Both the selectively bred rats and common-stock rats demonstrate "relapse" and an alcohol deprivation effect following 2 or more weeks of abstinence. Systemic administration of

  9. Toward an alcohol use disorder continuum using item response theory: results from the National Epidemiologic Survey on Alcohol and Related Conditions.

    PubMed

    Saha, Tulshi D; Chou, S Patricia; Grant, Bridget F

    2006-07-01

    Item response theory (IRT) was used to determine whether the DSM-IV diagnostic criteria for alcohol abuse and dependence are arrayed along a continuum of severity. Data came from a large nationally representative sample of the US population, 18 years and older. A two-parameter logistic IRT model was used to determine the severity and discrimination of each DSM-IV criterion. Differential criterion functioning (DCF) was also assessed across subgroups of the population defined by sex, age and race-ethnicity. All DSM-IV alcohol abuse and dependence criteria, except alcohol-related legal problems, formed a continuum of alcohol use disorder severity. Abuse and dependence criteria did not consistently tap the mildest or more severe end of the continuum respectively, and several criteria were identified as potentially redundant. The drinking in larger amounts or for longer than intended dependence criterion had the greatest discrimination and lowest severity than any other criterion. Although several criteria were found to function differentially between subgroups defined in terms of sex and age, there was evidence that the generalizability and validity of the criterion forming the continuum remained intact at the test score level. DSM-IV diagnostic criteria for alcohol abuse and dependence form a continuum of severity, calling into question the abuse-dependence distinction in the DSM-IV and the interpretation of abuse as a milder disorder than dependence. The criteria tapped the more severe end of the alcohol use disorder continuum, highlighting the need to identify other criteria capturing the mild to intermediate range of the severity. The drinking larger amounts or longer than intended dependence criterion may be a bridging criterion between drinking patterns that incur risk of alcohol use disorder at the milder end of the continuum, with tolerance, withdrawal, impaired control and serious social and occupational dysfunction at the more severe end of the alcohol use

  10. Alcohol use potentiates marijuana problem severity in young adult women.

    PubMed

    Stein, Michael D; Caviness, Celeste M; Anderson, Bradley J

    2014-01-01

    Most young adult women who smoke marijuana also drink alcohol. Marijuana-related problems are associated with marijuana use frequency. We hypothesized that increased alcohol use frequency potentiates the association between frequency of marijuana use and marijuana-related problem severity. We recruited women aged 18 to 24 who smoked marijuana at least monthly and were not treatment seeking. Marijuana and alcohol use were measured using the timeline follow-back method. Problems associated with marijuana use were assessed using the Marijuana Problems Scale. Participants (n = 332) averaged 20.5 ± 1.8 years of age, were 66.7% non-Hispanic White, and reported using marijuana on 51.5 ± 30.6 and alcohol on 18.9 ± 16.8 of the 90 previous days. Controlling for education, ethnicity, years of marijuana use, and other drug use, frequency of marijuana use (b = .22; p < .01) and frequency of alcohol use (b = 0.13; p < .05) had significant, positive effects on marijuana problem severity. In a separate multivariate model, the linear by linear interaction of marijuana by alcohol use frequency was significant (b = 0.18; p < .01), consistent with the hypothesis. Concurrent alcohol use impacts the experience of negative consequences from marijuana use in a community sample of young women. Discussions of marijuana use in young adults should consider the possible potentiating effects of alcohol use. Copyright © 2014 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

  11. Two case reports of oral ulcers with lamotrigine several weeks after oxcarbazepine withdrawal.

    PubMed

    O'Neill, Amy; de Leon, Jose

    2007-05-01

    To report two cases of mouth ulcers in lamotrigine patients after oxcarbazepine withdrawal. The first patient was a 35-year-old woman with bipolar disorder II (BD II) started on lamotrigine and tapered off oxcarbazepine while an inpatient. The second patient was a 36-year-old man with BD II. He was discharged on lamotrigine and oxcarbazepine with the recommendation of a slow withdrawal of oxcarbazepine. Many weeks after hospital discharge and after a stable lamotrigine dose had been established, both patients developed painful mouth ulcers that were diagnosed during outpatient visits. The first patient developed ulcers 39 days after oxcarbazepine was stopped and the ulcers resolved 4 days after lamotrigine discontinuation. The second patient was taking 1200 mg/day of oxcarbazepine and after leaving hospital decreased this to 600 mg/day. Twenty-two days after the oxcarbazepine decrease, he developed oral ulcers that resolved with oxcarbazepine and lamotrigine discontinuation. Lamotrigine is mainly metabolized by glucuronidation, specifically by the uridine 5'-diphosphate glucuronosyltransferases 1A4 (UGT1A4). Carbamazepine is a UGT1A4 inducer. These two cases suggest that oxcarbazepine may also induce lamotrigine metabolism. The discontinuation or dosage decrease of carbamazepine or oxcarbazepine may be associated with a slow increase of lamotrigine levels over several weeks and thus increase risk of lamotrigine toxicity that may manifest as oral ulcers. Hospital psychiatrists need to be aware that discontinuation of inducers may take several weeks to manifest as side effects.

  12. Diagnosis and Management of Alcoholic Liver Disease.

    PubMed

    Dugum, Mohannad; McCullough, Arthur

    2015-06-28

    Alcohol is a leading cause of liver disease and is associated with significant morbidity and mortality. Several factors, including the amount and duration of alcohol consumption, affect the development and progression of alcoholic liver disease (ALD). ALD represents a spectrum of liver pathology ranging from fatty change to fibrosis to cirrhosis. Early diagnosis of ALD is important to encourage alcohol abstinence, minimize the progression of liver fibrosis, and manage cirrhosis-related complications including hepatocellular carcinoma. A number of questionnaires and laboratory tests are available to screen for alcohol intake. Liver biopsy remains the gold-standard diagnostic tool for ALD, but noninvasive accurate alternatives, including a number of biochemical tests as well as liver stiffness measurement, are increasingly being utilized in the evaluation of patients with suspected ALD. The management of ALD depends largely on complete abstinence from alcohol. Supportive care should focus on treating alcohol withdrawal and providing enteral nutrition while managing the complications of liver failure. Alcoholic hepatitis (AH) is a devastating acute form of ALD that requires early recognition and specialized tertiary medical care. Assessment of AH severity using defined scoring systems is important to allocate resources and initiate appropriate therapy. Corticosteroids or pentoxifylline are commonly used in treating AH but provide a limited survival benefit. Liver transplantation represents the ultimate therapy for patients with alcoholic cirrhosis, with most transplant centers mandating a 6 month period of abstinence from alcohol before listing. Early liver transplantation is also emerging as a therapeutic measure in specifically selected patients with severe AH. A number of novel targeted therapies for ALD are currently being evaluated in clinical trials.

  13. Tobacco withdrawal among opioid-dependent smokers.

    PubMed

    Streck, Joanna M; Heil, Sarah H; Higgins, Stephen T; Bunn, Janice Y; Sigmon, Stacey C

    2018-04-01

    Prevalence of cigarette smoking among opioid-dependent individuals is 6-fold that of the general U.S. adult population and their quit rates are notoriously poor. One possible reason for the modest cessation outcomes in opioid-dependent smokers may be that they experience more severe tobacco withdrawal upon quitting. In this secondary analysis, we evaluated tobacco withdrawal in opioid-dependent (OD) smokers versus smokers without co-occurring substance use disorders (SUDs). Participants were 47 methadone- or buprenorphine-maintained smokers and 25 non-SUD smokers who completed 1 of several 2-week studies involving daily visits for biochemical monitoring, delivery of financial incentives contingent on smoking abstinence, and assessment of withdrawal via the Minnesota Nicotine Withdrawal Scale (MNWS). Prior to quitting smoking, OD smokers presented with higher baseline withdrawal scores than non-SUD smokers (1.7 ± 0.2 vs. 0.7 ± 0.2, respectively; F [1, 63] = 7.31, p < .001). Withdrawal scores in both groups decreased over the subsequent 2-week period with no group differences, F (1, 910) = 0.50, p = .48. A similar pattern was observed on craving (i.e., Desire to Smoke item of MNWS), although the trajectory of decrease over time on this item was also moderated by gender. Overall, there was no difference in withdrawal during biochemically verified smoking abstinence between OD and non-SUD smokers, suggesting that elevated withdrawal severity following quitting may not be a major factor contributing to the poor cessation outcomes consistently observed among OD smokers. Further scientific efforts are needed to improve our understanding of the high smoking rates and modest cessation outcomes in this challenging population. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  14. Change in psychiatric symptomatology after benfotiamine treatment in males is related to lifetime alcoholism severity.

    PubMed

    Manzardo, Ann M; Pendleton, Tiffany; Poje, Albert; Penick, Elizabeth C; Butler, Merlin G

    2015-07-01

    Severe alcoholism can be associated with significant nutritional and vitamin deficiency, especially vitamin B1 (thiamine) which is associated with neurological deficits impacting mood and cognition. Alcohol consumption was reduced among female but not male alcoholics after supplementation with the high potency thiamine analog benfotiamine (BF). We examined the relationship between lifetime alcoholism severity, psychiatric symptoms and response to BF among the alcohol dependent men from this cohort. Eighty-five adult men (mean age=48±8 years) meeting DSM-IV-TR criteria for a current alcohol use disorder who were abstinent <30days participated in a randomized, double-blind, placebo-controlled trial of 600mg BF vs placebo (PL) for 6 months. Psychometric testing included a derived Lifetime Alcoholism Severity Score (AS), Symptom Checklist 90R (SCL-90R), and the Barratt Impulsivity Scale (BIS) at baseline and at 6 months. Baseline SCL-90-R scale scores for men with high alcoholism severity (AS≥24; N=46 HAS) were significantly greater than for men with low alcoholism severity (AS<24; N=39 LAS), but BIS scores did not differ. MANOVA modeling at follow-up (N=50 completed subjects) identified a significant treatment effect (F=2.5, df=10, p<0.03) and treatment×alcoholism severity level interaction (F=2.5, dfnum=10, dfden=30, p<0.03) indicating reduced SCL-90-R scores among BF treated, HAS males. Above normal plasma thiamine levels at follow-up predicted reduced depression scores in a BF-treated subset (F=3.2, p<0.09, N=26). BF appears to reduce psychiatric distress and may facilitate recovery in severely affected males with a lifetime alcohol use disorder and should be considered for adjuvant therapy in alcohol rehabilitation. #NCT00680121 High Dose Vitamin B1 to Reduce Abusive Alcohol Use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Anxiety sensitivity and panic reactivity to bodily sensations: relation to quit-day (acute) nicotine withdrawal symptom severity among daily smokers making a self-guided quit attempt.

    PubMed

    Marshall, Erin C; Johnson, Kirsten; Bergman, Jenna; Gibson, Laura E; Zvolensky, Michael J

    2009-10-01

    The current investigation explored the main and interactive effects of panic attacks in response to laboratory-induced bodily sensations and anxiety sensitivity in predicting acute nicotine withdrawal symptoms among daily smokers making a self-guided quit attempt. Participants were 99 daily smokers (58% women; M(age) = 28.4 years, SD = 11.7) who completed a battery of questionnaires, a voluntary hyperventilation challenge, and a measure of nicotine withdrawal symptoms 12 hr after making a self-guided quit attempt. Results indicated that the interaction of anxiety sensitivity and panic responsivity to the challenge predicted quit-day nicotine withdrawal symptom severity above and beyond the main effects (p < .05). The form of the interaction indicated that the relationship between postchallenge panic attack status and acute nicotine withdrawal was more robust among individuals who were low in anxiety sensitivity. Individuals who did not experience a panic attack posthyperventilation who were also low in anxiety sensitivity reported the lowest levels of nicotine withdrawal. Results suggest that anxiety sensitivity may be less relevant with regard to acute nicotine withdrawal severity among individuals with panic-related problems.

  16. Does alcohol intoxication protect patients from severe injury and reduce hospital mortality? The association of alcohol consumption with the severity of injury and survival in trauma patients.

    PubMed

    Hsieh, Chi-Hsun; Su, Li-Ting; Wang, Yu-Chun; Fu, Chih-Yuan; Lo, Hung-Chieh; Lin, Chiu-Hsiu

    2013-12-01

    Alcohol-related motor vehicle collisions are a major cause of mortality in trauma patients. This prospective observational study investigated the influence of antecedent alcohol use on outcomes in trauma patients who survived to reach the hospital. From 2005 to 2011, all patients who were older than 18 years and were admitted as a result of motor vehicle crashes were included. Blood alcohol concentration (BAC) was routinely measured for each patient on admission. Patients were divided into four groups based on their BAC level, which included nondrinking, BAC less than 100, BAC 100 to 200, and BAC 200 mg/dL or greater. Patient demographics, physical status and injury severity on admission, length of hospital stay, and outcome were compared between the groups. Odds ratios of having a severe injury, prolonged hospital stay, and mortality were estimated. Patients with a positive BAC had an increased risk of sustaining craniofacial and thoracoabdominal injuries. Odds ratios of having severe injuries (Injury Severity Score [ISS] 16 or greater) and a prolonged hospital stay were also increased. However, for those patients whose ISS was 16 or greater and who also had a brain injury, risk of fatality was significantly reduced if they were intoxicated (BAC 200 mg/dL or greater) before injury. Alcohol consumption does not protect patients from sustaining severe injuries nor does it shorten the length of hospital stay. However, there were potential survival benefits related to alcohol consumption for patients with brain injuries but not for those without brain injuries. Additional research is required to investigate the mechanism of this association further.

  17. Management of precipitated opiate withdrawal syndrome induced by nalmefene mistakenly prescribed in opiate-dependent patients: a review for clinicians.

    PubMed

    Franchitto, Nicolas; Jullian, Benedicte; Salles, Juliette; Pelissier, Fanny; Rolland, Benjamin

    2017-06-01

    Nalmefene, a long-acting µ-opioid antagonist approved to treat alcohol use disorder, is occasionally mistakenly prescribed to opiate-dependent or opioid-treated patients. We review recent literature on drug-drug interactions between nalmefene and opioids that lead to precipitated opioid withdrawal, and focus on its management and planning for care at discharge. Areas covered: This article provides a brief and comprehensive review of management of precipitated opioid withdrawal syndrome when nalmefene is associated with an opioid, whether misused or legally prescribed. Expert opinion: When treating an opiate-dependent patient with co-occurring alcohol use disorder, both conditions need to be a focus of clinical attention. New drugs for alcohol use disorder have been approved, but must be given cautiously and with a full understanding of their potential drug-drug interactions with opioid medications. Opiate-dependent patients should be intensively monitored for risk factors of alcohol use disorder and should be continuously motivated for treatment maintenance. When nalmefene is administered to opiate-dependent patients, acute opioid withdrawal syndrome may occur. Management of precipitated acute opioid withdrawal may include short or long-acting µ-opioid agonists during hospitalization, in addition to supportive treatment. The best management of polydrug abusers is based on a multidisciplinary approach, which should be pursued and improved through continuing medical education.

  18. The Cannabis Withdrawal Scale development: patterns and predictors of cannabis withdrawal and distress.

    PubMed

    Allsop, David J; Norberg, Melissa M; Copeland, Jan; Fu, Shanlin; Budney, Alan J

    2011-12-01

    Rates of treatment seeking for cannabis are increasing, and relapse is common. Management of cannabis withdrawal is an important intervention point. No psychometrically sound measure for cannabis withdrawal exists, and as a result treatment developments cannot be optimally targeted. The aim is to develop and test the psychometrics of the Cannabis Withdrawal Scale and use it to explore predictors of cannabis withdrawal. A volunteer sample of 49 dependent cannabis users provided daily scores on the Cannabis Withdrawal Scale during a baseline week and 2 weeks of abstinence. Internal reliability (Cronbach's alpha=0.91), test-retest stability (average intra-class correlation=0.95) and content validity analysis show that the Cannabis Withdrawal Scale has excellent psychometric properties. Nightmares and/or strange dreams was the most valid item (Wald χ²=105.6, P<0.0001), but caused relatively little associated distress (Wald χ²=25.11, P=0.03). Angry outbursts were considered intense (Wald χ²=73.69, P<0.0001) and caused much associated distress (Wald χ²=45.54, P<0.0001). Trouble getting to sleep was also an intense withdrawal symptom (Wald χ²=42.31, P<0.0001) and caused significant associated distress (Wald χ²=47.76, P<0.0001). Scores on the Severity of Dependence Scale predicted cannabis withdrawal. The Cannabis Withdrawal Scale can be used as a diagnostic instrument in clinical and research settings where regular monitoring of withdrawal symptoms is required. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. Assessment of affective and somatic signs of ethanol withdrawal in C57BL/6J mice using a short-term ethanol treatment.

    PubMed

    Perez, E E; De Biasi, M

    2015-05-01

    Alcohol is one of the most prevalent addictive substances in the world. Withdrawal symptoms result from abrupt cessation of alcohol consumption in habitual drinkers. The emergence of both affective and physical symptoms produces a state that promotes relapse. Mice provide a preclinical model that could be used to study alcohol dependence and withdrawal while controlling for both genetic and environmental variables. The use of a liquid ethanol diet offers a reliable method for the induction of alcohol dependence in mice, but this approach is impractical when conducting high-throughput pharmacological screens or when comparing multiple strains of genetically engineered mice. The goal of this study was to compare withdrawal-associated behaviors in mice chronically treated with a liquid ethanol diet vs. mice treated with a short-term ethanol treatment that consisted of daily ethanol injections containing the alcohol dehydrogenase inhibitor, 4-methylpyrazole. Twenty-four hours after ethanol treatment, mice were tested in the open field arena, the elevated plus maze, the marble burying test, or for changes in somatic signs during spontaneous ethanol withdrawal. Anxiety-like and compulsive-like behaviors, as well as physical signs, were all significantly elevated in mice undergoing withdrawal, regardless of the route of ethanol administration. Therefore, a short-term ethanol treatment can be utilized as a screening tool for testing genetic and pharmacological agents before investing in a more time-consuming ethanol treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Effects of alcoholism severity and smoking on executive neurocognitive function.

    PubMed

    Glass, Jennifer M; Buu, Anne; Adams, Kenneth M; Nigg, Joel T; Puttler, Leon I; Jester, Jennifer M; Zucker, Robert A

    2009-01-01

    Neurocognitive deficits in chronic alcoholic men are well documented. Impairments include memory, visual-spatial processing, problem solving and executive function. The cause of impairment could include direct effects of alcohol toxicity, pre-existing cognitive deficits that predispose towards substance abuse, comorbid psychiatric disorders and abuse of substances other than alcohol. Cigarette smoking occurs at higher rates in alcoholism and has been linked to poor cognitive performance, yet the effects of smoking on cognitive function in alcoholism are often ignored. We examined whether chronic alcoholism and chronic smoking have effects on executive function. Alcoholism and smoking were examined in a community-recruited sample of alcoholic and non-alcoholic men (n = 240) using standard neuropsychological and reaction-time measures of executive function. Alcoholism was measured as the average level of alcoholism diagnoses across the study duration (12 years). Smoking was measured in pack-years. Both alcoholism and smoking were correlated negatively with a composite executive function score. For component measures, alcoholism was correlated negatively with a broad range of measures, whereas smoking was correlated negatively with measures that emphasize response speed. In regression analyses, both smoking and alcoholism were significant predictors of executive function composite. However, when IQ is included in the regression analyses, alcoholism severity is no longer significant. Both smoking and alcoholism were related to executive function. However, the effect of alcoholism was not independent of IQ, suggesting a generalized effect, perhaps affecting a wide range of cognitive abilities of which executive function is a component. On the other hand, the effect of smoking on measures relying on response speed were independent of IQ, suggesting a more specific processing speed deficit associated with chronic smoking.

  1. Insight into alcohol-related problems and its associations with severity of alcohol consumption, mental health status, race, and level of acculturation in southern Taiwanese indigenous people with alcoholism.

    PubMed

    Yen, Cheng-Fang; Hsiao, Ray C; Ries, Richard; Liu, Shu-Chun; Huang, Chi-Fen; Chang, Yu-Ping; Yu, Ming-Lung

    2008-01-01

    While not well known in the West, Taiwan has a substantial indigenous population, and this population has rapidly developed alcohol problems. This study examined the level of insight into alcohol-related problems and its associations with the severity of alcohol consumption, mental health status, race, and the level of acculturation among indigenous populations with alcohol problems in southern Taiwan. A total of 332 indigenes, whose total Alcohol Use Disorders Identification Test (AUDIT) score was equal to 8 or higher, were interviewed. The associations between the level of insight into alcohol-related problems and the severity of alcohol drinking on the AUDIT, mental health status on the Chinese Health Questionnaire-12 (>or= 4 vs. < 4), race (Bunun vs. non-Bunun), and the level of acculturation on the Taiwan Aboriginal Acculturation Scale were examined using logistic regression models. The results of this study found that 72.6% of the participants had poor insight into alcohol-related problems and no participant had good insight. Participants who had more severe alcohol drinking or poor mental health were more likely to have a higher level of insight into alcohol-related problems. Participants who were non-Bunun were also more likely to have a higher level of insight into alcohol-related problems, but the level of acculturation was not associated with the level of insight into alcohol-related problems. These findings suggest that most alcoholic indigenes in southern Taiwan have poor insight into their own alcohol-related problems. Cultural specific interventions targeting and improving the indigenes' insight into alcohol-related problems are needed.

  2. Quantitative trait locus gene mapping: a new method for locating alcohol response genes.

    PubMed

    Crabbe, J C

    1996-01-01

    Alcoholism is a multigenic trait with important non-genetic determinants. Studies with genetic animal models of susceptibility to several of alcohol's effects suggest that several genes contributing modest effects on susceptibility (Quantitative Trait Loci, or QTLs) are important. A new technique of QTL gene mapping has allowed the identification of the location in mouse genome of several such QTLs. The method is described, and the locations of QTLs affecting the acute alcohol withdrawal reaction are described as an example of the method. Verification of these QTLs in ancillary studies is described and the strengths, limitations, and future directions to be pursued are discussed. QTL mapping is a promising method for identifying genes in rodents with the hope of directly extrapolating the results to the human genome. This review is based on a paper presented at the First International Congress of the Latin American Society for Biomedical Research on Alcoholism, Santiago, Chile, November 1994.

  3. 27 CFR 19.420 - Withdrawals of spirits without payment of tax for experimental or research use.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Withdrawals of spirits without payment of tax for experimental or research use. A scientific university, college of learning, or institution of scientific research qualified under § 19.35 may withdraw spirits... without payment of tax for experimental or research use. 19.420 Section 19.420 Alcohol, Tobacco Products...

  4. Causes, types and severity of injury among army soldiers hospitalized with alcohol comorbidity.

    PubMed

    Howland, Jonathan; Bell, Nicole S; Hollander, Ilyssa E

    2007-09-01

    To examine the relationship between alcohol use and the cause, type and severity of hospitalized injuries. We used the Total Army Injury and Health Outcomes Database (TAIHOD) to conduct cross-sectional analyses of the association between alcohol comorbidity and the cause, type and severity of soldiers' non-combat injuries requiring hospitalization. Subjects were active-duty US army soldiers (n = 211 790) hospitalized with a primary diagnosis of injury between 1980 and 2002. Alcohol comorbidity was positively associated with hospitalized injuries resulting from fights and falls and negatively associated with sports injuries; positively associated with hospitalized cases of head injury, open wounds and poisonings and negatively associated with musculoskeletal injury; and, overall, associated with shorter length of stay. Controlling for demographic factors did not moderate the association between alcohol and cause, type or severity of injury. Alcohol comorbidity is specifically associated with injuries related to impairment and antisocial behavior.

  5. Perinatal risk factors and social withdrawal behaviour.

    PubMed

    Guedeney, Antoine; Marchand-Martin, Laetitia; Cote, Sylvana J; Larroque, Béatrice

    2012-04-01

    The objectives of the study were (1) to assess prevalence of social withdrawal behaviour in infants aged 12 months included in the French Perinatal Risk Factor Study Eden; (2) To study the correlation between relational withdrawal and several perinatal and parental factors assessed in the EDEN study. A longitudinal study using the ADBB scale was conducted within the Eden Cohort in the year 2008. 1,586 infants were included in the study. Fourteen percent of the children who had an ADBB assessment had a score at 5 and over on the ADBB, a scale designed to assess social withdrawal behaviour at age 0-24 months. Social withdrawal at 12 months was associated with low birth weight, low gestational age and with intra uterine growth retardation. Social withdrawal was independently associated with several maternal and paternal risk factors. The level of social withdrawal behaviour increased with a score of maternal difficulties. This study on a large longitudinally followed volunteer sample demonstrate a clear association of social withdrawal behaviour at age one with low birth weight and preterm birth, possibly mediated by parental vulnerabilities. Social withdrawal behaviour seems to be an important alarm signal to detect early on particularly in premature and small for date babies. © Springer-Verlag 2012

  6. Effects of alcohol on platelet functions.

    PubMed

    Renaud, S C; Ruf, J C

    1996-03-15

    Recent epidemiologic studies have consistently shown that moderate intake of alcoholic beverages protect against morbidity and mortality from coronary heart disease and ischemic stroke. By contrast, alcohol drinking may also predispose to cerebral hemorrhage. These observations suggest an effect of alcohol similar to that of aspirin. Several studies in humans and animals have shown that the immediate effect of alcohol, either added in vitro to platelets or 10 to 20 min after ingestion, is to decrease platelet aggregation in response to most agonists (thrombin, ADP, epinephrine, collagen). Several hours later, as, in free-living populations deprived of drinking since the previous day it is mostly secondary aggregation to ADP and epinephrine and aggregation to collagen that are still inhibited in alcohol drinkers. By contrast, in binge drinkers or in alcoholics after alcohol withdrawal, response to aggregation, especially that induced by thrombin, is markedly increased. This rebound phenomenon, easily reproduced in rats, may explain ischemic strokes or sudden death known to occur after episodes of drunkenness. The platelet rebound effect of alcohol drinking was not observed with moderate red wine consumption in man. The protection afforded by wine has been recently duplicated in rats by grape tannins added to alcohol. This protection was associated with a decrease in the level of conjugated dienes, the first step in lipid peroxidation. In other words, wine drinking does not seem to be associated with the increased peroxidation usually observed with spirit drinking. Although further studies are required, the platelet rebound effect of alcohol drinking could be associated with an excess of lipid peroxides known to increase platelet reactivity, especially to thrombin.

  7. Alcohol Use Severity Among Adult Hispanic Immigrants: Examining the Roles of Family Cohesion, Social Support, and Gender.

    PubMed

    Cano, Miguel Ángel; Sánchez, Mariana; Rojas, Patria; Ramírez-Ortiz, Daisy; Polo, Katherine L; Romano, Eduardo; De La Rosa, Mario

    2018-03-21

    This study examined (a) the direct association of family cohesion on alcohol use severity among adult Hispanic immigrants; (b) the indirect association of family cohesion on alcohol use severity via social support; and (c) if gender moderates the direct and indirect associations between family cohesion and alcohol use severity. Mediation and moderation analyses were conducted on a cross-sectional sample of 411 (men = 222, women = 189) participants from Miami-Dade, Florida. Findings indicate that higher family cohesion was directly associated with higher social support and lower alcohol use severity. Higher social support was also directly associated with lower alcohol use severity. Additionally, family cohesion had an indirect association with alcohol use severity via social support. Moderation analyses indicated that gender moderated the direct association between family cohesion and alcohol use severity, but did not moderate the indirect association. Some potential clinical implications may be that strengthening family cohesion may enhance levels of social support, and in turn, lower alcohol use severity among adult Hispanic immigrants. Furthermore, strengthening family cohesion may be especially beneficial to men in efforts to lower levels of alcohol use severity.

  8. Thirst for living of alcoholic patients: medical care's experience.

    PubMed

    Augeraud, Emmanuel; Puertolas, Christian; Rouchon, Dominique

    2004-01-01

    The medical care lavished on terminal and on alcoholic patients leads us to observe an analogy between these two life paths. This raises a question: do links exist between these two conditions? We will present Mr. B's record with alcohol. Analysing alcohol withdrawal allows us to show that during withdrawal, after having experienced similar stages to those described by Kübler-Ross, the alcoholic patient is in a grieving process. When abstinent, Mr. B faces two possibilities: either the grief is incomplete and the drive towards alcohol leads him to die to life; or he remains abstinent, with the help sometimes of what we call 'support dyads'. All this presupposes that the initial stages of dying to alcohol, followed by a psychic work of dis-fusion, have been brought to a successful conclusion. Links do exist between these two life paths, in the sense that these stages enable them to face the major trauma of their lives, e.g. alcoholism and serious illness.

  9. Causes, types and severity of injury among army soldiers hospitalized with alcohol comorbidity*

    PubMed Central

    Howland, Jonathan; Bell, Nicole S.; Hollander, Ilyssa E.

    2007-01-01

    Aim To examine the relationship between alcohol use and the cause, type and severity of hospitalized injuries. Design/setting We used the Total Army Injury and Health Outcomes Database (TAIHOD) to conduct cross-sectional analyses of the association between alcohol comorbidity and the cause, type and severity of soldiers’ non-combat injuries requiring hospitalization. Participants Subjects were active-duty US army soldiers (n = 211 790) hospitalized with a primary diagnosis of injury between 1980 and 2002. Findings Alcohol comorbidity was positively associated with hospitalized injuries resulting from fights and falls and negatively associated with sports injuries; positively associated with hospitalized cases of head injury, open wounds and poisonings and negatively associated with musculoskeletal injury; and, overall, associated with shorter length of stay. Controlling for demographic factors did not moderate the association between alcohol and cause, type or severity of injury. Conclusion Alcohol comorbidity is specifically associated with injuries related to impairment and antisocial behavior. PMID:17697276

  10. Severe lactic acidosis following alcohol related generalised seizures.

    PubMed

    Hulme, J; Sherwood, N

    2004-12-01

    A 45-year-old alcoholic man presented following several short grand-mal seizures. He was not known to be epileptic. Initial investigations demonstrated a severe lactic acidosis. The rise in lactate was one of the highest levels reported in similar patients. The patient recovered within 4 h of management with oxygen, fluids and sodium bicarbonate. Lactic acidosis following convulsions is often associated with spontaneous resolution and a favourable outcome.

  11. Epigenetics—Beyond the Genome in Alcoholism

    PubMed Central

    Starkman, Bela G.; Sakharkar, Amul J.; Pandey, Subhash C.

    2012-01-01

    Genetic and environmental factors play a role in the development of alcoholism. Whole-genome expression profiling has highlighted the importance of several genes that may contribute to alcohol abuse disorders. In addition, more recent findings have added yet another layer of complexity to the overall molecular mechanisms involved in a predisposition to alcoholism and addiction by demonstrating that processes related to genetic factors that do not manifest as DNA sequence changes (i.e., epigenetic processes) play a role. Both acute and chronic ethanol exposure can alter gene expression levels in specific neuronal circuits that govern the behavioral consequences related to tolerance and dependence. The unremitting cycle of alcohol consumption often includes satiation and self-medication with alcohol, followed by excruciating withdrawal symptoms and the resultant relapse, which reflects both the positive and negative affective states of alcohol addiction. Recent studies have indicated that behavioral changes induced by acute and chronic ethanol exposure may involve chromatin remodeling resulting from covalent histone modifications and DNA methylation in the neuronal circuits involving a brain region called the amygdala. These findings have helped identify enzymes involved in epigenetic mechanisms, such as the histone deacetylase, histone acetyltransferase, and DNA methyltransferase enzymes, as novel therapeutic targets for the development of future pharmacotherapies for the treatment of alcoholism. PMID:23134045

  12. Epigenetics-beyond the genome in alcoholism.

    PubMed

    Starkman, Bela G; Sakharkar, Amul J; Pandey, Subhash C

    2012-01-01

    Genetic and environmental factors play a role in the development of alcoholism. Whole-genome expression profiling has highlighted the importance of several genes that may contribute to alcohol abuse disorders. In addition, more recent findings have added yet another layer of complexity to the overall molecular mechanisms involved in a predisposition to alcoholism and addiction by demonstrating that processes related to genetic factors that do not manifest as DNA sequence changes (i.e., epigenetic processes) play a role. Both acute and chronic ethanol exposure can alter gene expression levels in specific neuronal circuits that govern the behavioral consequences related to tolerance and dependence. The unremitting cycle of alcohol consumption often includes satiation and self-medication with alcohol, followed by excruciating withdrawal symptoms and the resultant relapse, which reflects both the positive and negative affective states of alcohol addiction. Recent studies have indicated that behavioral changes induced by acute and chronic ethanol exposure may involve chromatin remodeling resulting from covalent histone modifications and DNA methylation in the neuronal circuits involving a brain region called the amygdala. These findings have helped identify enzymes involved in epigenetic mechanisms, such as the histone deacetylase, histone acetyltransferase, and DNA methyltransferase enzymes, as novel therapeutic targets for the development of future pharmacotherapies for the treatment of alcoholism.

  13. Label-Free Proteomic Analysis of Protein Changes in the Striatum during Chronic Ethanol Use and Early Withdrawal

    PubMed Central

    Ayers-Ringler, Jennifer R.; Oliveros, Alfredo; Qiu, Yanyan; Lindberg, Daniel M.; Hinton, David J.; Moore, Raymond M.; Dasari, Surendra; Choi, Doo-Sup

    2016-01-01

    The molecular mechanisms underlying the neuronal signaling changes in alcohol addiction and withdrawal are complex and multifaceted. The cortico-striatal circuit is highly implicated in these processes, and the striatum plays a significant role not only in the early stages of addiction, but in the developed-addictive state as well, including withdrawal symptoms. Transcriptional analysis is a useful method for determining changes in gene expression, however, the results do not always accurately correlate with protein levels. In this study, we employ label-free proteomic analysis to determine changes in protein expression within the striatum during chronic ethanol use and early withdrawal. The striatum, composed primarily of medium spiny GABAergic neurons, glutamatergic and dopaminergic nerve terminals and astrocytes, is relatively homogeneous for proteomic analysis. We were able to analyze more than 5000 proteins from both the dorsal (caudate and putamen) and ventral (nucleus accumbens) striatum and identified significant changes following chronic intermittent ethanol exposure and acute (8 h) withdrawal compared to ethanol naïve and ethanol exposure groups respectively. Our results showed significant changes in proteins involved in glutamate and opioid peptide signaling, and also uncovered novel pathways including mitochondrial function and lipid/cholesterol metabolism, as revealed by changes in electron transport chain proteins and RXR activation pathways. These results will be useful in the development of novel treatments for alcohol withdrawal and thereby aid in recovery from alcohol use disorder. PMID:27014007

  14. Sequence variations of the human MPDZ gene and association with alcoholism in subjects with European ancestry.

    PubMed

    Karpyak, Victor M; Kim, Jeong-Hyun; Biernacka, Joanna M; Wieben, Eric D; Mrazek, David A; Black, John L; Choi, Doo-Sup

    2009-04-01

    Mpdz gene variations are known contributors of acute alcohol withdrawal severity and seizures in mice. To investigate the relevance of these findings for human alcoholism, we resequenced 46 exons, exon-intron boundaries, and 2 kilobases in the 5' region of the human MPDZ gene in 61 subjects with a history of alcohol withdrawal seizures (AWS), 59 subjects with a history of alcohol withdrawal without AWS, and 64 Coriell samples from self-reported nonalcoholic subjects [all European American (EA) ancestry] and compared with the Mpdz sequences of 3 mouse strains with different propensity to AWS. To explore potential associations of the human MPDZ gene with alcoholism and AWS, single SNP and haplotype analyses were performed using 13 common variants. Sixty-seven new, mostly rare variants were discovered in the human MPDZ gene. Sequence comparison revealed that the human gene does not have variations identical to those comprising Mpdz gene haplotype associated with AWS in mice. We also found no significant association between MPDZ haplotypes and AWS in humans. However, a global test of haplotype association revealed a significant difference in haplotype frequencies between alcohol-dependent subjects without AWS and Coriell controls (p = 0.015), suggesting a potential role of MPDZ in alcoholism and/or related phenotypes other than AWS. Haplotype-specific tests for the most common haplotypes (frequency > 0.05), revealed a specific high-risk haplotype (p = 0.006, maximum statistic p = 0.051), containing rs13297480G allele also found to be significantly more prevalent in alcoholics without AWS compared with nonalcoholic Coriell subjects (p = 0.019). Sequencing of MPDZ gene in individuals with EA ancestry revealed no variations in the sites identical to those associated with AWS in mice. Exploratory haplotype and single SNP association analyses suggest a possible association between the MPDZ gene and alcohol dependence but not AWS. Further functional genomic analysis of MPDZ

  15. The `One-Two Punch' of Alcoholism: Role of Central Amygdala Dynorphins / Kappa-Opioid Receptors

    PubMed Central

    Kissler, Jessica L.; Sirohi, Sunil; Reis, Daniel J.; Jansen, Heiko T.; Quock, Raymond M.; Smith, Daniel G.; Walker, Brendan M.

    2013-01-01

    Background The dynorphin (DYN)/κ-opioid receptor (KOR) system undergoes neuroadaptations following chronic alcohol exposure that promote excessive operant self-administration and negative affective-like states; however, the exact mechanisms are unknown. The present studies tested the hypothesis that an upregulated DYN/KOR system mediates excessive alcohol self-administration that occurs during withdrawal in alcohol-dependent rats by assessing DYN A peptide expression and KOR function, in combination with site-specific pharmacological manipulations. Methods Male Wistar rats were trained to self-administer alcohol using operant behavioral strategies and subjected to intermittent alcohol vapor- or air-exposure. Changes in self-administration were assessed by pharmacological challenges during acute withdrawal. In addition, 22-kHz ultrasonic vocalizations were utilized to measure negative affective-like states. Immunohistochemical techniques assessed DYN A peptide expression and [35S]GTPγS coupling assays were performed to assess KOR function. Results Alcohol-dependent rats displayed increased alcohol self-administration, negative affective-like behavior, DYN A-like immunoreactivity and KOR signaling in the amygdala compared to non-dependent controls. Site-specific infusions of a KOR antagonist selectively attenuated self-administration in dependent rats whereas, a MOR/DOR antagonist cocktail selectively reduced self-administration in non-dependent rats. A MOR antagonist/partial KOR agonist attenuated self-administration in both cohorts. Conclusion Increased DYN A and increased KOR signaling could set the stage for a `one-two punch' during withdrawal that drives excessive alcohol consumption in alcohol-dependence. Importantly, intra-CeA pharmacological challenges functionally confirmed a DYN/KOR system involvement in the escalated alcohol self-administration. Together, the DYN/KOR system is heavily dysregulated in alcohol dependence and contributes to the excessive

  16. Role for the satiety factor Oleoylethanolamide in alcoholism

    PubMed Central

    Bilbao, Ainhoa; Serrano, Antonia; Cippitelli, Andrea; Pavón, Francisco J.; Giuffrida, Andrea; Suárez, Juan; García-Marchena, Nuria; Baixeras, Elena; de Heras, Raquel Gomez; Ciccocioppo, Roberto; Cravatt, Benjamin F.; Parsons, Loren H.; Piomelli, Daniele; de Fonseca, Fernando Rodríguez

    2015-01-01

    Oleoylethanolamide (OEA) is a satiety factor released by the gut that controls motivational responses for caloric foods. Here, using both, rat and mice models, we determined that the administration of alcohol releases OEA that, by engaging peroxisome proliferator-activated receptor alpha (PPARα), reduces alcohol consumption. Animals lacking FAAH, the enzyme that degrades OEA, accumulates this lipid in response to ethanol and displayed reduced alcohol preference. Pharmacological administration of OEA reduced operant alcohol self-administration via a peripheral mechanism, since this effect was abrogated by chemical deafferentation with capsaicin. Intracerebral injection of PPARα agonists did not affect alcohol self-administration. OEA also abolished both, cue-induced reinstatement of alcohol self-administration and the enhancement of alcohol consumption induced by a period of alcohol deprivation, suggesting a role for OEA on alcohol relapse. In addition, animals fed with a liquid diet containing 10% alcohol displayed elevated plasma levels of OEA that decreases upon removal of alcohol in the diet. This decrease paralleled the onset of alcohol withdrawal (AWD) symptoms and the administration of OEA reduced the severity of AWD. Finally, OEA, by inhibiting the expression of lipogenic enzymes, reduces chronic alcohol-induced liver steatosis, an effect not observed in PPARα-deficient mice. These results link OEA to the homeostatic adaption to alcohol and opens new opportunities for the treatment of alcoholism. PMID:26037332

  17. 29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a mass...

  18. 29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 9 2011-07-01 2011-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a mass...

  19. Phenibut (β-Phenyl-γ-aminobutyric Acid) Dependence and Management of Withdrawal: Emerging Nootropics of Abuse.

    PubMed

    Ahuja, Tania; Mgbako, Ofole; Katzman, Caroline; Grossman, Allison

    2018-01-01

    This case report describes the development of withdrawal from phenibut, a gamma-aminobutyric acid-receptor type B agonist. Although phenibut is not an FDA-approved medication, it is available through online retailers as a nootropic supplement. There are reports of dependence in patients that misuse phenibut. We report a case in which a patient experienced withdrawal symptoms from phenibut and was successfully treated with a baclofen taper. This case report highlights the development of phenibut use disorder with coingestion of alcohol and potential management for phenibut withdrawal. We believe clinicians must be aware of how phenibut dependence may present and how to manage the withdrawal syndrome.

  20. Acute oral administration of the novel, competitive and selective glucocorticoid receptor antagonist ORG 34517 reduces the severity of ethanol withdrawal and related hypothalamic- pituitary-adrenal axis activation

    PubMed Central

    Reynolds, Anna R.; Saunders, Meredith A.; Brewton, Honoree’ W.; Winchester, Sydney R.; Elgumati, Ibrahim S.; Prendergast, Mark A.

    2015-01-01

    Background The development of ethanol dependence is associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis and activation of type II glucocorticoid receptors (GR). These effects may contribute to withdrawal-associated anxiety, craving and relapse to drinking. The present studies examined acute and oral administration of the novel, selective and competitive GR antagonist ORG 34517 on the severity of ethanol withdrawal. Methods Adult, male Sprague-Dawley rats were administered ethanol (4g/kg/i.g.) twice daily for 5 days followed by 2 days of withdrawal for 1, 2 or 3 consecutive cycles. Blood ethanol levels (BELs) were determined at 0930 on Day 4 of each week, while blood corticosterone levels (BCLs) were obtained at 1100 hrs on the first day of each ethanol withdrawal. During early withdrawal, subjects received oral administration of ORG 345617 (60 mg/kg/i.g.) or a placebo and withdrawal was monitored. Results Peak BELs of 225.52 mg/dl were observed during the third week. Withdrawal from three cycles of the regimen produced marked behavioral abnormalities (e.g. aggression, rigidity, and hypoactivity) and significant increases in BCLs of ethanol-dependent subjects. Acute, oral administration of ORG 34517 during early withdrawal significantly reduced both the severity of ethanol withdrawal, as reflected in reduced rigidity, aggression, and hypoactivity, and elevations in BCL without producing any sedative-like effects. Conclusions The present findings demonstrate that repeated ethanol exposure and withdrawal is associated with significant behavioral abnormalities and dysregulation of HPA axis activation. Further these data suggest that selective GR antagonists should be further considered as putative pharmacotherapies for treatment of ethanol dependence. PMID:26143299

  1. Acute oral administration of the novel, competitive and selective glucocorticoid receptor antagonist ORG 34517 reduces the severity of ethanol withdrawal and related hypothalamic-pituitary-adrenal axis activation.

    PubMed

    Reynolds, Anna R; Saunders, Meredith A; Brewton, Honoree' W; Winchester, Sydney R; Elgumati, Ibrahim S; Prendergast, Mark A

    2015-09-01

    The development of ethanol dependence is associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis and activation of type II glucocorticoid receptors (GR). These effects may contribute to withdrawal-associated anxiety, craving and relapse to drinking. The present studies examined acute and oral administration of the novel, selective and competitive GR antagonist ORG 34517 on the severity of ethanol withdrawal. Adult, male Sprague-Dawley rats were administered ethanol (4g/kg/i.g.) twice daily for 5 days followed by 2 days of withdrawal for 1, 2 or 3 consecutive cycles. Blood ethanol levels (BELs) were determined at 0930 on Day 4 of each week, while blood corticosterone levels (BCLs) were obtained at 11:00hours on the first day of each ethanol withdrawal. During early withdrawal, subjects received oral administration of ORG 345617 (60mg/kg/i.g.) or a placebo and withdrawal was monitored. Peak BELs of 225.52mg/dl were observed during the third week. Withdrawal from three cycles of the regimen produced marked behavioral abnormalities (e.g., aggression, rigidity, and hypoactivity) and significant increases in BCLs of ethanol-dependent subjects. Acute, oral administration of ORG 34517 during early withdrawal significantly reduced both the severity of ethanol withdrawal, as reflected in reduced rigidity, aggression, and hypoactivity, and elevations in BCL without producing any sedative-like effects. The present findings demonstrate that repeated ethanol exposure and withdrawal is associated with significant behavioral abnormalities and dysregulation of HPA axis activation. Further these data suggest that selective GR antagonists should be further considered as putative pharmacotherapies for treatment of ethanol dependence. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Withdrawal Symptoms and Nicotine Dependence Severity Predict Virtual Reality Craving in Cigarette-Deprived Smokers

    PubMed Central

    Cooper, Kim N.; Mahoney, James J.; Bordnick, Patrick S.; Salas, Ramiro; Kosten, Thomas R.; Dani, John A.; De La Garza, Richard

    2015-01-01

    Introduction: Virtual reality (VR) has been shown to be effective in eliciting responses to nicotine cues in cigarette smokers. The primary aim of this study was to investigate whether cigarette-deprived smokers would exhibit increased craving and changes in heart rate when viewing cigarette related cues as compared to non-smoking cues in a VR environment, and the secondary aim was to assess the extent to which self-assessed measures of withdrawal and dependence correlated with VR craving. Methods: Nicotine-dependent cigarette smokers were recruited for a 2 day study. On Day 1, participants smoked as usual and on Day 2 were deprived from smoking overnight. On both days, participants completed self-assessment questionnaires on withdrawal, craving, and nicotine-dependence. Participants completed a VR session during the cigarette deprivation condition only (Day 2). During this session, they were exposed to active smoking and placebo (non-smoking) cues. Results: The data show that self-reported levels of “craving” (p < .01) and “thinking about cigarettes” (p < .0001) were significantly greater after exposure to the active cues versus non-smoking cues. Significant increases in heart rate were found for 3 of 4 active cues when compared to non-smoking cues (p < .05). Finally, significant positive correlations were found between self-reported craving prior to the VR session and craving induced by active VR cues (p < .01). Conclusions: In this report, active VR cues elicited craving during cigarette deprivation. This is the first study to demonstrate that self-reported craving, withdrawal symptoms, and nicotine dependence severity predict cue-induced craving in the VR setting. PMID:25475087

  3. Childhood maltreatment severity and alcohol use in adult psychiatric inpatients: The mediating role of emotion regulation difficulties.

    PubMed

    Dutcher, Christina D; Vujanovic, Anka A; Paulus, Daniel J; Bartlett, Brooke A

    2017-09-01

    Emotion regulation difficulties are a potentially key mechanism underlying the association between childhood maltreatment and alcohol use in adulthood. The current study examined the mediating role of emotion regulation difficulties in the association between childhood maltreatment severity (i.e., Childhood Trauma Questionnaire total score) and past-month alcohol use severity, including alcohol consumption frequency and alcohol-related problems (i.e., number of days of alcohol problems, ratings of "bother" caused by alcohol problems, ratings of treatment importance for alcohol problems). Participants included 111 acute-care psychiatric inpatients (45.0% female; Mage=33.5, SD=10.6), who reported at least one DSM-5 posttraumatic stress disorder Criterion A traumatic event, indexed via the Life Events Checklist for DSM-5. Participants completed questionnaires regarding childhood maltreatment, emotion regulation difficulties, and alcohol use. A significant indirect effect of childhood maltreatment severity via emotion regulation difficulties in relation to alcohol use severity (β=0.07, SE=0.04, 99% CI [0.01, 0.21]) was documented. Specifically, significant indirect effects were found for childhood maltreatment severity via emotion regulation difficulties in relation to alcohol problems (β's between 0.05 and 0.12; all 99% bootstrapped CIs with 10,000 resamples did not include 0) but not alcohol consumption. Emotion regulation difficulties may play a significant role in the association between childhood maltreatment severity and alcohol outcomes. Clinical implications are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. The Role of GABAA Receptors in the Development of Alcoholism

    PubMed Central

    Enoch, Mary-Anne

    2008-01-01

    Alcoholism is a common, heritable, chronic relapsing disorder. GABAA receptors undergo allosteric modulation by ethanol, anesthetics, benzodiazepines and neurosteroids and have been implicated in the acute as well as the chronic effects of ethanol including tolerance, dependence and withdrawal. Medications targeting GABAA receptors ameliorate the symptoms of acute withdrawal. Ethanol induces plasticity in GABAA receptors: tolerance is associated with generally decreased GABAA receptor activation and differentially altered subunit expression. The dopamine (DA) mesolimbic reward pathway originating in the ventral tegmental area (VTA), and interacting stress circuitry play an important role in the development of addiction. VTA GABAergic interneurons are the primary inhibitory regulators of DA neurons and a subset of VTA GABAA receptors may be implicated in the switch from heavy drinking to dependence. GABAA receptors modulate anxiety and response to stress; important elements of sustained drinking and relapse. The GABAA receptor subunit genes clustered on chromosome 4 are highly expressed in the reward pathway. Several recent studies have provided strong evidence that one of these genes, GABRA2, is implicated in alcoholism in humans. The influence of the interaction between ethanol and GABAA receptors in the reward pathway on the development of alcoholism together with genetic and epigenetic vulnerabilities will be explored in this review. PMID:18440057

  5. A STUDY ON THE COPING BEHAVIOURS OF WIVES OF ALCOHOLICS

    PubMed Central

    Rao, T.S. Sathyanarayana; Kuruvilla, K.

    1992-01-01

    A study was conducted on 30 wives of alcoholics using Orford-Guthrie's ‘coping with drinking’ questionnaire. Tlie commonest coping behaviour reported was discord, avoidance, indulgence and fearful withdrawal while marital breakdown, taking special action, assertion and sexual withdrawal were least frequent. There was no significant correlation between the coping behaviours and the variables like duration of marriage, duration of husband’s alcoholism, socio-economic and educational status. Implications of these findings are discussed and a cross cultural comparison is made. PMID:21776145

  6. Modulation of alcohol preference by NMDA antagonists in male rats.

    PubMed

    Lamblin, F; Deuceuninck, D; De Witte, P

    1993-11-01

    Chronic alcoholization by alcohol inhalation was used to study the properties of magnesium, a non-competitive NMDA receptor antagonist, and CGP 39551, a competitive NMDA receptor antagonist, on behavioural dependence as estimated by the free-choice paradigm [alcohol 10% (v/v) vs. water], on the hypermotility after alcohol withdrawal, and finally on the cortical vascularization. The first experimental group received the drugs per os during the whole alcoholization period. Magnesium (20 mg/kg/day) decreased the alcohol dependence while CGP 39551 (5 and 10 mg/kg/day) increased, in a dose-dependent manner, the dependence to alcohol. A second group of animals received the same drugs at the same dosages, not simultaneously during chronic alcoholization, but immediately after alcoholization in one shot i.p. injection. In this case, rats receiving 5 mg/kg CGP 39551 never showed any dependence towards alcohol, while 10 mg/kg CGP 39551 or 20 mg/kg magnesium prolonged the number of days of alcohol dependence. These results thus indicate the close interaction between NMDA receptor function and dependence for alcohol. Magnesium had no effects on hypermotility, while CGP 39551-treated animals presented a decrease in the hypermotility observed after alcohol withdrawal. Neither drug affected the hypervascularization accompanying the chronic alcoholization.

  7. Development of Ethanol Withdrawal-Related Sensitization and Relapse Drinking in Mice Selected for High or Low Ethanol Preference

    PubMed Central

    Lopez, Marcelo F.; Grahame, Nicholas J.; Becker, Howard C.

    2010-01-01

    Background Previous studies have shown that high alcohol consumption is associated with low withdrawal susceptiblility, while at the same time, other studies have shown that exposure to ethanol vapor increases alcohol drinking in rats and mice. In the present studies, we sought to shed light on this seeming contradiction by using mice selectively bred for High- (HAP) and Low- (LAP) Alcohol Preference, first, assessing these lines for differences in signs of ethanol withdrawal and second, for differences in the efficacy of intermittent alcohol vapor exposure on elevating subsequent ethanol intake. Methods Experiment 1 examined whether these lines of mice differed in ethanol withdrawal-induced CNS hyperexcitability and the development of sensitization to this effect following intermittent ethanol vapor exposure. Adult HAP and LAP lines (replicates 1 and 2), and the C3H/HeNcr inbred strain (included as a control genotype for comparison purposes) received intermittent exposure to ethanol vapor and were evaluated for ethanol withdrawal-induced seizures assessed by scoring handling-induced convulsions (HIC). Experiment 2 examined the influence of chronic intermittent ethanol exposure on voluntary ethanol drinking. Adult male and female HAP-2 and LAP-2 mice, along with male C57BL/6J (included as comparative controls) were trained to drink 10% ethanol using a limited access (2 hr/day) 2-bottle choice paradigm. After stable baseline daily intake was established, mice received chronic intermittent ethanol vapor exposure in inhalation chambers. Ethanol intake sessions resumed 72 hr after final ethanol (or air) exposure for 5 consecutive days. Results Following chronic ethanol treatment, LAP mice exhibited overall greater withdrawal seizure activity compared to HAP mice. In Experiment 2, chronic ethanol exposure/withdrawal resulted in a significant increase in ethanol intake in male C57BL/6J, and modestly elevated intake in HAP-2 male mice. Ethanol intake for male control mice

  8. Binge alcohol drinking elicits persistent negative affect in mice.

    PubMed

    Lee, Kaziya M; Coehlo, Michal; McGregor, Hadley A; Waltermire, Ryan S; Szumlinski, Karen K

    2015-09-15

    Cessation from chronic alcohol abuse often produces a dysphoric state that can persist into protracted withdrawal. This dysphoric state is theorized to function as a negative reinforcer that maintains excessive alcohol consumption and/or precipitates relapse in those struggling to abstain from alcohol. However, we know relatively little regarding the impact of cessation from binge drinking on behavioral measures of negative affect and related neurobiology. Male C57BL/6J mice were given access to unsweetened 20% alcohol for 6 weeks under modified Drinking-in-the-dark procedures, followed by behavioral testing beginning either 1 or 21 days into withdrawal. Mice were administered a behavioral test battery consisting of: the elevated plus maze, light/dark box, novel object test, marble burying test, Porsolt forced swim test and sucrose preference test to assess anxiogenic and depressive signs. Egr1 immunostaining was used to quantify cellular activity within the central nucleus of the amygdala (CEA), basolateral amygdala (BLA), bed nucleus of the stria terminalis (BNST), and the nucleus accumbens (Acb) shell (AcbSh) and core (AcbC). Compared to water controls, alcohol-drinking mice exhibited higher indices of emotionality in the majority of behavioral assays. The hyper-emotionality exhibited by binge drinking mice was apparent at both withdrawal time-points and correlated with higher Egr1+ cell counts in the CEA and BNST, compared to controls. These data show that affective symptoms emerge very early after cessation of binge drinking and persist into protracted withdrawal. A history of binge drinking is capable of producing enduring neuroadaptations within brain circuits mediating emotional arousal. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. The current situation of treatment systems for alcoholism in Korea.

    PubMed

    Kim, Jee Wook; Lee, Boung Chul; Kang, Tae-Cheon; Choi, Ihn-Geun

    2013-02-01

    Alcoholism is becoming one of the most serious issues in Korea. The purpose of this review article was to understand the present status of the treatment system for alcoholism in Korea compared to the United States and to suggest its developmental direction in Korea. Current modalities of alcoholism treatment in Korea including withdrawal treatment, pharmacotherapy, and psychosocial treatment are available according to Korean evidence-based treatment guidelines. Benzodiazepines and supportive care including vitamin and nutritional support are mainly used to treat alcohol withdrawal in Korea. Naltrexone and acamprosate are the drugs of first choice to treat chronic alcoholism. Psychosocial treatment methods such as individual psychotherapy, group psychotherapy, family therapy, cognitive behavior therapy, cue exposure therapy, 12-step facilitation therapy, self-help group therapy, and community-based treatment have been carried out to treat chronic alcoholism in Korea. However, current alcohol treatment system in Korea is not integrative compared to that in the United States. To establish the treatment system, it is important to set up an independent governmental administration on alcohol abuse, to secure experts on alcoholism, and to conduct outpatient alcoholism treatment programs and facilities in an open system including some form of continuing care.

  10. The Current Situation of Treatment Systems for Alcoholism in Korea

    PubMed Central

    Kim, Jee Wook; Lee, Boung Chul; Kang, Tae-Cheon

    2013-01-01

    Alcoholism is becoming one of the most serious issues in Korea. The purpose of this review article was to understand the present status of the treatment system for alcoholism in Korea compared to the United States and to suggest its developmental direction in Korea. Current modalities of alcoholism treatment in Korea including withdrawal treatment, pharmacotherapy, and psychosocial treatment are available according to Korean evidence-based treatment guidelines. Benzodiazepines and supportive care including vitamin and nutritional support are mainly used to treat alcohol withdrawal in Korea. Naltrexone and acamprosate are the drugs of first choice to treat chronic alcoholism. Psychosocial treatment methods such as individual psychotherapy, group psychotherapy, family therapy, cognitive behavior therapy, cue exposure therapy, 12-step facilitation therapy, self-help group therapy, and community-based treatment have been carried out to treat chronic alcoholism in Korea. However, current alcohol treatment system in Korea is not integrative compared to that in the United States. To establish the treatment system, it is important to set up an independent governmental administration on alcohol abuse, to secure experts on alcoholism, and to conduct outpatient alcoholism treatment programs and facilities in an open system including some form of continuing care. PMID:23400047

  11. Quantifying the Clinical Significance of Cannabis Withdrawal

    PubMed Central

    Allsop, David J.; Copeland, Jan; Norberg, Melissa M.; Fu, Shanlin; Molnar, Anna; Lewis, John; Budney, Alan J.

    2012-01-01

    Background and Aims Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt. Methods and Results A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p = 0.0001). Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p = 0.03). Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p = 0.001). Conclusions Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes. PMID:23049760

  12. Alcohol hangover symptoms and their contribution to the overall hangover severity.

    PubMed

    Penning, Renske; McKinney, Adele; Verster, Joris C

    2012-01-01

    Scientific literature suggests a large number of symptoms that may be present the day after excessive alcohol consumption. The purpose of this study was to explore the presence and severity of hangover symptoms, and determine their interrelationship. A survey was conducted among n = 1410 Dutch students examining their drinking behavior and latest alcohol hangover. The severity of 47 presumed hangover symptoms were scored on a 10-point scale ranging from 0 (absent) to 10 (maximal). Factor analysis was conducted to summarize the data into groups of associated symptoms that contribute significantly to the alcohol hangover and symptoms that do not. About half of the participants (56.1%, n = 791) reported having had a hangover during the past month. Most commonly reported and most severe hangover symptoms were fatigue (95.5%) and thirst (89.1%). Factor analysis revealed 11 factors that together account for 62% of variance. The most prominent factor 'drowsiness' (explained variance 28.8%) included symptoms such as drowsiness, fatigue, sleepiness and weakness. The second factor 'cognitive problems' (explained variance 5.9%) included symptoms such as reduced alertness, memory and concentration problems. Other factors, including the factor 'disturbed water balance' comprising frequently reported symptoms such as 'dry mouth' and 'thirst', contributed much less to the overall hangover (explained variance <5%). Drowsiness and impaired cognitive functioning are the two dominant features of alcohol hangover.

  13. Withdrawal Symptoms and Nicotine Dependence Severity Predict Virtual Reality Craving in Cigarette-Deprived Smokers.

    PubMed

    Thompson-Lake, Daisy G Y; Cooper, Kim N; Mahoney, James J; Bordnick, Patrick S; Salas, Ramiro; Kosten, Thomas R; Dani, John A; De La Garza, Richard

    2015-07-01

    Virtual reality (VR) has been shown to be effective in eliciting responses to nicotine cues in cigarette smokers. The primary aim of this study was to investigate whether cigarette-deprived smokers would exhibit increased craving and changes in heart rate when viewing cigarette related cues as compared to non-smoking cues in a VR environment, and the secondary aim was to assess the extent to which self-assessed measures of withdrawal and dependence correlated with VR craving. Nicotine-dependent cigarette smokers were recruited for a 2 day study. On Day 1, participants smoked as usual and on Day 2 were deprived from smoking overnight. On both days, participants completed self-assessment questionnaires on withdrawal, craving, and nicotine-dependence. Participants completed a VR session during the cigarette deprivation condition only (Day 2). During this session, they were exposed to active smoking and placebo (non-smoking) cues. The data show that self-reported levels of "craving" (p < .01) and "thinking about cigarettes" (p < .0001) were significantly greater after exposure to the active cues versus non-smoking cues. Significant increases in heart rate were found for 3 of 4 active cues when compared to non-smoking cues (p < .05). Finally, significant positive correlations were found between self-reported craving prior to the VR session and craving induced by active VR cues (p < .01). In this report, active VR cues elicited craving during cigarette deprivation. This is the first study to demonstrate that self-reported craving, withdrawal symptoms, and nicotine dependence severity predict cue-induced craving in the VR setting. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Alcohol and violence: neuropeptidergic modulation of monoamine systems

    PubMed Central

    Miczek, Klaus A.; DeBold, Joseph F.; Hwa, Lara S.; Newman, Emily L.; de Almeida, Rosa M. M.

    2015-01-01

    Neurobiological processes underlying the epidemiologically-established link between alcohol and several types of social, aggressive, and violent behavior remain poorly understood. Acute low doses of alcohol, as well as withdrawal from long-term alcohol use, may lead to escalated aggressive behavior in a subset of individuals. An urgent task will be to disentangle the host of interacting genetic and environmental risk factors in individuals that are predisposed to engage in escalated aggressive behavior. The modulation of 5-hydroxytryptamine impulse flow by gamma-aminobutyric acid (GABA) and glutamate, acting via distinct ionotropic and metabotropic receptor subtypes in the dorsal raphe nucleus during alcohol consumption, is of critical significance in the suppression and escalation of aggressive behavior. In anticipation and reaction to aggressive behavior, neuropeptides such as corticotropin-releasing factor, neuropeptide Y, opioid peptides, and vasopressin interact with monoamines, GABA, and glutamate to attenuate and amplify aggressive behavior in alcohol-consuming individuals. These neuromodulators represent novel molecular targets for intervention that await clinical validation. Intermittent episodes of brief social defeat during aggressive confrontations are sufficient to cause long-lasting neuroadaptations that can lead to the escalation of alcohol consumption. PMID:26285061

  15. Linkage analyses of cannabis dependence, craving, and withdrawal in the San Francisco Family Study

    PubMed Central

    Ehlers, Cindy L.; Gizer, Ian R.; Vieten, Cassandra; Wilhelmsen, Kirk C.

    2010-01-01

    Cannabis is the most widely used illicit drug in the United States. There is ample evidence that cannabis use has a heritable component, yet the genes underlying cannabis use disorders are yet to be completely identified. This study's aims were to map susceptibility loci for cannabis use and dependence and two narrower cannabis-related phenotypes of “craving” and “withdrawal” using a family study design. Participants were 2524 adults participating in the University of California San Francisco (UCSF) Family Alcoholism Study. DSM-IV diagnoses of cannabis dependence, as well as indices of cannabis craving and withdrawal, were obtained using a modified version of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). Genotypes were determined for a panel of 791 microsatellite polymorphisms. Multipoint variance component LOD scores were obtained using SOLAR. Genome-wide significance for linkage (LOD > 3.0) was not found for the DSM-IV cannabis dependence diagnosis, however, linkage analyses of cannabis “craving” and the cannabis withdrawal symptom of “nervous, tense, restless or irritable” revealed five sites with LOD scores over 3.0 on chromosomes 1, 3, 6, 7, 9. These results identify new regions of the genome associated with cannabis use phenotypes as well as corroborate the importance of several chromosome regions highlighted in previous linkage analyses for other substance dependence phenotypes. PMID:19937978

  16. Glutamatergic targets for new alcohol medications

    PubMed Central

    Spanagel, Rainer; Krystal, John H.

    2013-01-01

    Rationale An increasingly compelling literature points to a major role for the glutamate system in mediating the effects of alcohol on behavior and the pathophysiology of alcoholism. Preclinical studies indicate that glutamate signaling mediates certain aspects of ethanol’s intoxicating and rewarding effects, and undergoes adaptations following chronic alcohol exposure that may contribute to the withdrawal, craving and compulsive drug-seeking that drive alcohol abuse and alcoholism. Objectives We discuss the potential for targeting the glutamate system as a novel pharmacotherapeutic approach to treating alcohol use disorders, focusing on five major components of the glutamate system: the N-methyl-D-aspartate (NMDA) receptor and specific NMDA subunits, the glycineB site on the NMDA receptors (NMDAR), L-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid ionotropic (AMPA) and kainate (KAR) receptors, metabotropic receptors (mGluR), and glutamate transporters. Results Chronic alcohol abuse produces a hyperglutamatergic state, characterized by elevated extracellular glutamate and altered glutamate receptors and transporters. Pharmacologically manipulating glutamatergic neurotransmission alters alcohol-related behaviors including intoxication, withdrawal, and alcohol-seeking, in rodents and human subjects. Blocking NMDA and AMPA receptors reduces alcohol consumption in rodents, but side-effects may limit this as a therapeutic approach. Selectively targeting NMDA and AMPA receptor subunits (e.g., GluN2B, GluA3), or the NMDAR glycineB site offers an alternative approach. Blocking mGluR5 potently affects various alcohol-related behaviors in rodents, and mGluR2/3 agonism also suppresses alcohol consumption. Finally, glutamate transporter upregulation may mitigate behavioral and neurotoxic sequelae of excess glutamate caused by alcohol. Conclusions Despite the many challenges that remain, targeting the glutamate system offers genuine promise for developing new

  17. Corticosteroids, nutrition, pentoxifylline, or fecal microbiota transplantation for severe alcoholic hepatitis.

    PubMed

    Philips, Cyriac Abby; Phadke, Nikhil; Ganesan, Karthik; Ranade, Shatakshi; Augustine, Philip

    2018-06-21

    Alcohol-induced intestinal dysbiosis is central to the development of the severe alcoholic liver disease. We present the first study to compare outcomes in patients of severe alcoholic hepatitis (SAH) on nutritional therapy, corticosteroids, pentoxifylline, and healthy donor fecal transplantation (FMT) and discuss distinct microbial community and microbiome metabolic functional changes after FMT. Out of 1271 liver disease patients, 809 (63.7%) were diagnosed to have the alcoholic liver disease, of which 51 patients (8 treated with corticosteroids, 17 with nutritional support only, 10 with pentoxifylline, 16 receiving FMT) were included. Clinical, biochemical parameters, liver disease, and alcoholic hepatitis severity scores at baseline and mortality at the end of 1 and 3 months were analyzed between groups. Stool microbiota (SM) analysis was performed for healthy controls (HC) and respective recipients after FMT. All the patients were male. The proportions of patients surviving at the end of 1 and 3 months in the steroids, nutrition, pentoxifylline, and FMT group were 63%, 47%, 40% and 75% [p = 0.179] and 38%, 29%, 30%, and 75% [p = 0.036], respectively. When compared with FMT, relative risk and hazard ratios for death were higher in all the other groups. Following FMT, distinct and beneficial modulation of SM and pathways of dysregulated metabolism, infections, inflammation, and oxidative stress in SAH patients were noted in tandem with improved clinical outcomes. Healthy donor FMT for SAH improves survival beyond what is offered by current therapies and can function as a cost-effective bridge to liver transplant (LT) or for improving transplant-free survival. Larger studies and randomized trials are unmet needs.

  18. Blood biomarkers of Hikikomori, a severe social withdrawal syndrome.

    PubMed

    Hayakawa, Kohei; Kato, Takahiro A; Watabe, Motoki; Teo, Alan R; Horikawa, Hideki; Kuwano, Nobuki; Shimokawa, Norihiro; Sato-Kasai, Mina; Kubo, Hiroaki; Ohgidani, Masahiro; Sagata, Noriaki; Toda, Hiroyuki; Tateno, Masaru; Shinfuku, Naotaka; Kishimoto, Junji; Kanba, Shigenobu

    2018-02-13

    Hikikomori, a severe form of social withdrawal syndrome, is a growing social issue in Japan and internationally. The pathophysiology of hikikomori has not yet been elucidated and an effective treatment remains to be established. Recently, we revealed that avoidant personality disorder is the most common comorbidity of hikikomori. Thus, we have postulated that avoidant personality is the personality underpinning hikikomori. First, we herein show relationships between avoidant personality traits, blood biomarkers, hikikomori-related psychological features, and behavioural characteristics assessed by a trust game in non-hikikomori volunteers. Avoidant personality traits were negatively associated with high-density lipoprotein cholesterol (HDL-C) and uric acid (UA) in men, and positively associated with fibrin degeneration products (FDP) and high sensitivity C-reactive protein (hsCRP) in women. Next, we recruited actual individuals with hikikomori, and compared avoidant personality traits, blood biomarkers, and psychological features between individuals with hikikomori and age-matched healthy controls. Individuals with hikikomori had higher avoidant personality scores in both sexes, and showed lower serum UA levels in men and lower HDL-C levels in women compared with healthy controls. This is the first report showing possible blood biomarkers for hikikomori, and opens the door to clarify the underlying biological pathophysiology of hikikomori.

  19. The role of GABA(A) receptors in the development of alcoholism.

    PubMed

    Enoch, Mary-Anne

    2008-07-01

    Alcoholism is a common, heritable, chronic relapsing disorder. GABA(A) receptors undergo allosteric modulation by ethanol, anesthetics, benzodiazepines and neurosteroids and have been implicated in the acute as well as the chronic effects of ethanol including tolerance, dependence and withdrawal. Medications targeting GABA(A) receptors ameliorate the symptoms of acute withdrawal. Ethanol induces plasticity in GABA(A) receptors: tolerance is associated with generally decreased GABA(A) receptor activation and differentially altered subunit expression. The dopamine (DA) mesolimbic reward pathway originating in the ventral tegmental area (VTA), and interacting stress circuitry play an important role in the development of addiction. VTA GABAergic interneurons are the primary inhibitory regulators of DA neurons and a subset of VTA GABA(A) receptors may be implicated in the switch from heavy drinking to dependence. GABA(A) receptors modulate anxiety and response to stress; important elements of sustained drinking and relapse. The GABA(A) receptor subunit genes clustered on chromosome 4 are highly expressed in the reward pathway. Several recent studies have provided strong evidence that one of these genes, GABRA2, is implicated in alcoholism in humans. The influence of the interaction between ethanol and GABA(A) receptors in the reward pathway on the development of alcoholism together with genetic and epigenetic vulnerabilities will be explored in this review.

  20. Intensity of care and withdrawal of life-sustaining therapies in severe traumatic brain injury patients: a post-hoc analysis of a multicentre retrospective cohort study.

    PubMed

    Gerges, Peter R A; Moore, Lynne; Léger, Caroline; Lauzier, François; Shemilt, Michèle; Zarychanski, Ryan; Scales, Damon C; Burns, Karen E A; Bernard, Francis; Zygun, David; Neveu, Xavier; Turgeon, Alexis F

    2018-06-14

    The intensity of care provided to critically ill patients has been shown to be associated with mortality. In patients with traumatic brain injury (TBI), specialized neurocritical care is often required, but whether it affects clinically significant outcomes is unknown. We aimed to determine the association of the intensity of care on mortality and the incidence of withdrawal of life-sustaining therapies in critically ill patients with severe TBI. We conducted a post hoc analysis of a multicentre retrospective cohort study of critically ill adult patients with severe TBI. We defined the intensity of care as a daily cumulative sum of interventions during the intensive care unit stay. Our outcome measures were all-cause hospital mortality and the incidence of withdrawal of life-sustaining therapies. Seven hundred sixteen severe TBI patients were included in our study. Most were male (77%) with a mean (standard deviation) age of 42 (20.5) yr and a median [interquartile range] Glasgow Coma Scale score of 3 [3-6]. Our results showed an association between the intensity of care and mortality (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.63 to 0.74) and the incidence of withdrawal of life-sustaining therapy (HR, 0.73; 95% CI, 0.67 to 0.79). In general, more intense care was associated with fewer deaths and a lower incidence of withdrawal of life-sustaining therapies in critically ill patients with severe TBI.

  1. Barbiturates for the treatment of alcohol withdrawal syndrome: A systematic review of clinical trials.

    PubMed

    Mo, Yoonsun; Thomas, Michael C; Karras, George E

    2016-04-01

    To perform a systematic review of the clinical trials concerning the use of barbiturates for the treatment of acute alcohol withdrawal syndrome (AWS). A literature search of MEDLINE, EMBASE, and the Cochrane Library, together with a manual citation review was conducted. We selected English-language clinical trials (controlled and observational studies) evaluating the efficacy and safety of barbiturates compared with benzodiazepine (BZD) therapy for the treatment of AWS in the acute care setting. Data extracted from the included trials were duration of delirium, number of seizures, length of intensive care unit and hospital stay, cumulated doses of barbiturates and BZDs, and respiratory or cardiac complications. Seven studies consisting of 4 prospective controlled and 3 retrospective trials were identified. Results from all the included studies suggest that barbiturates alone or in combination with BZDs are at least as effective as BZDs in the treatment of AWS. Furthermore, barbiturates appear to have acceptable tolerability and safety profiles, which were similar to those of BZDs in patients with AWS. Although the evidence is limited, based on our findings, adding phenobarbital to a BZD-based regimen is a reasonable option, particularly in patients with BZD-refractory AWS. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Theoretical Frameworks and Mechanistic Aspects of Alcohol Addiction: Alcohol Addiction as a Reward Deficit Disorder

    PubMed Central

    2012-01-01

    Alcoholism can be defined by a compulsion to seek and take drug, loss of control in limiting intake, and the emergence of a negative emotional state when access to the drug is prevented. Alcoholism impacts multiple motivational mechanisms and can be conceptualized as a disorder that includes a progression from impulsivity (positive reinforcement) to compulsivity (negative reinforcement). The compulsive drug seeking associated with alcoholism can be derived from multiple neuroadaptations, but the thesis argued here is that a key component involves the construct of negative reinforcement. Negative reinforcement is defined as drug taking that alleviates a negative emotional state. The negative emotional state that drives such negative reinforcement is hypothesized to derive from dysregulation of specific neurochemical elements involved in reward and stress within the basal forebrain structures involving the ventral striatum and extended amygdala, respectively. Specific neurochemical elements in these structures include not only decreases in reward neurotransmission, such as decreased dopamine and γ-aminobutyric acid function in the ventral striatum, but also recruitment of brain stress systems, such as corticotropin-releasing factor (CRF), in the extended amygdala. Acute withdrawal from chronic alcohol, sufficient to produce dependence, increases reward thresholds, increases anxiety-like responses, decreases dopamine system function, and increases extracellular levels of CRF in the central nucleus of the amygdala. CRF receptor antagonists also block excessive drug intake produced by dependence. A brain stress response system is hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence, and to contribute to the compulsivity of alcoholism. Other components of brain stress systems in the extended amygdala that interact with CRF and that may contribute to the negative motivational state

  3. An integrative analysis of ethanol tolerance and withdrawal in zebrafish (Danio rerio)

    PubMed Central

    Tran, Steven; Chatterjee, Diptendu; Gerlai, Robert

    2014-01-01

    The zebrafish is emerging as a popular animal model for alcohol (ethanol or EtOH) addiction due to its simplicity and practical advantages. Two phenomena associated with ethanol addiction are the development of tolerance and withdrawal. Using a multi-level approach in the current study, we characterize ethanol tolerance and withdrawal in zebrafish. We first investigate the temporal trajectory of ethanol concentration in the zebrafish brain in response to an acute exposure and during withdrawal. We report that ethanol concentrations approach a steady state within 60 minutes of exposure to 0.50% and 1.00% v/v ethanol and rapidly decline and return to zero within 60 minutes following withdrawal from chronic ethanol exposure (0.50% v/v). We characterize the changes associated with ethanol tolerance and withdrawal in zebrafish by focusing on 3 domains relevant to ethanol addiction: motor patterns, physiological responses (i.e. cortisol levels), and neurochemical alterations. The use of multiple domains of investigation allowed an in-depth analysis of ethanol induced changes in zebrafish. PMID:24598276

  4. A dose for the wiser is enough: the alcohol benefits for associative learning in zebrafish.

    PubMed

    Chacon, Diana M; Luchiari, Ana C

    2014-08-04

    This study aimed to test seeking behavior caused by alcohol and the drug effects on learning in the zebrafish, Danio rerio. Three treatments were conducted: acute, chronic and withdrawal, using 0.10%, 0.25%, and 1.00% alcohol and control (0.00%) (vol/vol.%). For the drug seeking behavior, we used a place preference paradigm (shuttle box tank) before and after alcohol exposure in acute (single exposure) and chronic (7 days) treatments. We observed a change in the basal preference due to the association with alcohol only for 0.25% and 1.00% doses in both acute and chronic offering, indicating an alcohol-seeking behavior after the drug exposure. For the learning task, two treatments were tested: chronic alcohol exposure (26 days including the learning period) and alcohol withdrawal (15 days of alcohol exposure before the learning period). During the learning period, fish received light stimulus followed by food in a pre-defined area of the tank for 8 consecutive days. The low dose group (0.10%) learned the task by the 3rd day both in chronic and withdrawal treatments. The higher doses (0.25% and 1.00%) caused a learning impairment in the chronic treatment group, while fish from the alcohol withdrawal treatment displayed learning on the final testing day. Therefore, we suggest that high alcohol doses impair learning and cause drug seeking behavior, even after drug exposure cessation, while low doses positively affect learning and do not cause seeking behavior. Given our results we propose that the zebrafish is a promising model for identifying active compounds, antibodies or genes which modulate the alcohol dual effects: learning improvement and reinforcing behavior. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Rates of past-year alcohol treatment across two time metrics and differences by alcohol use disorder severity and mental health comorbidities

    PubMed Central

    Evans-Polce, Rebecca; Schuler, Megan S.

    2016-01-01

    Introduction Little is known about how alcohol treatment rates vary across age or years since onset of an alcohol use disorder (AUD). We examined past-year treatment prevalence and associations across these important time metrics. Method Data on 22,278 adults ages 18–50 were from the National Epidemiologic Survey on Alcohol and Related Conditions-III (2012–2013). We examined the age-varying prevalence of alcohol treatment and associations of past-year AUD severity, MDD status, and DUD status with treatment. Additionally, for individuals with a lifetime AUD (N=7,089), we examined associations of severity, MDD, and DUD across years since AUD onset. Results Individuals with Moderate/Severe past-year AUD had significantly higher treatment rates at nearly all ages, compared to those with Mild or no AUD. For those with Moderate/Severe AUD, treatment rates were highest during late adolescence and middle adulthood and lowest during early adulthood. Mental health comorbidities were positively associated with treatment at certain age ranges in mid-adulthood. Among individuals with a lifetime AUD, those with Moderate/Severe past-year AUD had significantly higher past-year treatment rates across all years since onset. MDD and DUD were both positively associated with treatment at nearly all years since AUD onset. Conclusions Alcohol treatment rates varied notably by age and, to a lesser extent, by years since AUD onset. Greater AUD severity was consistently associated with higher rates of treatment, whereas Mild AUD had a much weaker relationship. MDD and DUD showed similar patterns of positive association with treatment. Our results highlight important subgroups where unmet treatment needs are highest. PMID:27475284

  6. Alcohol, cardiac arrhythmias and sudden death.

    PubMed

    Kupari, M; Koskinen, P

    1998-01-01

    Studies in experimental animals have shown varying and apparently opposite effects of alcohol on cardiac rhythm and conduction. Given acutely to non-alcoholic animals, ethanol may even have anti-arrhythmic properties whereas chronic administration clearly increases the animals' susceptibility to cardiac arrhythmias. Chronic heavy alcohol use has been incriminated in the genesis of cardiac arrhythmias in humans. The evidence has come from clinical observations, retrospective case-control studies, controlled studies of consecutive admissions for arrhythmias, and prospective epidemiological investigations. Furthermore, electrophysiological studies have shown that acute alcohol administration facilitates the induction of tachyarrhythmias in selected heavy drinkers. The role of alcohol appears particularly conspicuous in idiopathic atrial fibrillation. Occasionally, ventricular tachyarrhythmias have also been provoked by alcohol intake. Several lines of evidence suggest that heavy drinking increases the risk of sudden cardiac death with fatal arrhythmia as the most likely mechanism. According to epidemiological studies this effect appears most prominent in middle-aged men and is only partly explained by confounding traits such as smoking and social class. The basic arrhythmogenic effects of alcohol are still insufficiently delineated. Subclinical heart muscle injury from chronic heavy use may be instrumental in producing patchy delays in conduction. The hyperadrenergic state of drinking and withdrawal may also contribute, as may electrolyte abnormalities, impaired vagal heart rate control, repolarization abnormalities with prolonged QT intervals and worsening of myocardial ischaemia or sleep apnoea. Most of what we know about alcohol and arrhythmias relates to heavy drinking. The effect of social drinking on clinical arrhythmias in non-alcoholic cardiac patients needs to be addressed further.

  7. Behavioral Actions of Alcohol: Phenotypic Relations from Multivariate Analysis of Mutant Mouse Data

    PubMed Central

    Blednov, Yuri A.; Mayfield, R. Dayne; Belknap, John; Harris, R. Adron

    2012-01-01

    Behavioral studies of genetically diverse mice have proven powerful for determining relationships between phenotypes and have been widely used in alcohol research. Most of these studies rely on naturally occurring genetic polymorphisms among inbred strains and selected lines. Another approach is to introduce variation by engineering single gene mutations in mice. We have tested 37 different mutant mice and their wild type controls for a variety (31) of behaviors and have mined this dataset by K-means clustering and analysis of correlations. We found a correlation between a stress-related response (activity in a novel environment) and alcohol consumption and preference for saccharin. We confirmed several relationships detected in earlier genetic studies including positive correlation of alcohol consumption with saccharin consumption, and negative correlations with conditioned taste aversion and alcohol withdrawal severity. Introduction of single gene mutations either eliminated or greatly diminished these correlations. The three tests of alcohol consumption used (continuous two bottle choice, and two limited access tests: Drinking In the Dark and Sustained High Alcohol Consumption) share a relationship with saccharin consumption, but differ from each other in their correlation networks. We suggest that alcohol consumption is controlled by multiple physiological systems where single gene mutations can disrupt the networks of such systems. PMID:22405477

  8. Behavioral Economic Measures of Alcohol Reward Value as Problem Severity Indicators in College Students

    PubMed Central

    Skidmore, Jessica R.; Murphy, James G.; Martens, Matthew P.

    2014-01-01

    The aims of the current study were to examine the associations among behavioral economic measures of alcohol value derived from three distinct measurement approaches, and to evaluate their respective relations with traditional indicators of alcohol problem severity in college drinkers. Five behavioral economic metrics were derived from hypothetical demand curves that quantify reward value by plotting consumption and expenditures as a function of price, another metric measured proportional behavioral allocation and enjoyment related to alcohol versus other activities, and a final metric measured relative discretionary expenditures on alcohol. The sample included 207 heavy drinking college students (53% female) who were recruited through an on-campus health center or university courses. Factor analysis revealed that the alcohol valuation construct comprises two factors: one factor that reflects participants’ levels of alcohol price sensitivity (demand persistence), and a second factor that reflects participants’ maximum consumption and monetary and behavioral allocation towards alcohol (amplitude of demand). The demand persistence and behavioral allocation metrics demonstrated the strongest and most consistent multivariate relations with alcohol-related problems, even when controlling for other well-established predictors. The results suggest that behavioral economic indices of reward value show meaningful relations with alcohol problem severity in young adults. Despite the presence of some gender differences, these measures appear to be useful problem indicators for men and women. PMID:24749779

  9. Factor Analysis and Psychometric Properties of the Minnesota Nicotine Withdrawal Scale and the Minnesota Nicotine Withdrawal Scale-Revised: Italian Version.

    PubMed

    Svicher, Andrea; Beghè, Agnese; Mangiaracina, Giacomo; Cosci, Fiammetta

    2017-01-01

    We run Exploratory and Confirmatory Factor Analyses of the Minnesota Nicotine Withdrawal Scale (MNWS) and of the MNWS-Revised (MNWS-R). Psychometric properties were also explored. Adult Italian smokers, 366 in all, were assessed via the MNWS-R together with rating scales measuring cigarette dependence, alcohol use, anxiety sensitivity and negative affect at baseline and after 3 months. The MNWS showed good psychometric properties (α = 0.85; rtt = 0.59) and a unidimensional factor structure. The 2-factor model of MNWS-R had the best fit and the factors were labelled psychological symptoms (α = 0.86; rtt = 0.59) and associated somatic features (α = 0.64; rtt = 0.45). MNWS showed 1 factor; MNWS-R showed 2 relatively dependent factors. The results need to be replicated in smokers in withdrawal. © 2017 S. Karger AG, Basel.

  10. Impaired affective prosody decoding in severe alcohol use disorder and Korsakoff syndrome.

    PubMed

    Brion, Mélanie; de Timary, Philippe; Mertens de Wilmars, Serge; Maurage, Pierre

    2018-06-01

    Recognizing others' emotions is a fundamental social skill, widely impaired in psychiatric populations. These emotional dysfunctions are involved in the development and maintenance of alcohol-related disorders, but their differential intensity across emotions and their modifications during disease evolution remain underexplored. Affective prosody decoding was assessed through a vocalization task using six emotions, among 17 patients with severe alcohol use disorder, 16 Korsakoff syndrome patients (diagnosed following DSM-V criteria) and 19 controls. Significant disturbances in emotional decoding, particularly for negative emotions, were found in alcohol-related disorders. These impairments, identical for both experimental groups, constitute a core deficit in excessive alcohol use. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Effect of Withinia Somnifera and Shilajit on Alcohol Addiction in Mice

    PubMed Central

    Bansal, Priya; Banerjee, Sugato

    2016-01-01

    Background: Alcohol addiction is a social problem leading to both loss of health and economic prosperity among addicted individuals. Common properties of anti-addictive compounds include anti-anxiety, anticonvulsants, anti-depressant, and nootropic actions primarily through modulation of gamma-aminobutyric acid (GABA) and serotonergic systems. Objective: Here, we screen ashwagandha and shilajit known ethnopharmacologically as nervine tonic and adaptogenic herbs for possible anti-addictive potential. Materials and Methods: Effect of ashwagandha churna and shilajit was measured on ethanol withdrawal anxiety using elevated plus maze. Role of ashwagandha and shilajit on chronic ethanol consumption (21 days) was measured using two bottle choice protocol of voluntary drinking. We also measured the effect of the above herbs on corticohippocampal GABA, dopamine, and serotonin levels. Results: Both ashwagandha and shilajit were found to reduce alcohol withdrawal anxiety in a dose-dependent manner. These herbs alone or in combination also decreased ethanol intake and increased water intake significantly after 21 days of chronic administration. Chronic administration of ashwagandha was found to significantly increase GABA and serotonin levels whereas shilajit altered cortico-hippocampal dopamine in mice. Conclusion: These central nervous system active herbs alone or in combination reduced both alcohol dependence and withdrawal thus showing promising anti-addictive potential. SUMMARY Withinia Somnifera alone and in combination with Shilajeet prevented ethanol withdrawal and alcohol addiction Abbreviations used: GABA: Gama aminobutyric acid, CNS: Central Nervous System, CPP:Condition place preference, DA: Dopamine, 5-HT: 5-hydroxytryptamine, NMDA:N-methyl-D-aspartate PMID:27279696

  12. Effect of Withinia Somnifera and Shilajit on Alcohol Addiction in Mice.

    PubMed

    Bansal, Priya; Banerjee, Sugato

    2016-05-01

    Alcohol addiction is a social problem leading to both loss of health and economic prosperity among addicted individuals. Common properties of anti-addictive compounds include anti-anxiety, anticonvulsants, anti-depressant, and nootropic actions primarily through modulation of gamma-aminobutyric acid (GABA) and serotonergic systems. Here, we screen ashwagandha and shilajit known ethnopharmacologically as nervine tonic and adaptogenic herbs for possible anti-addictive potential. Effect of ashwagandha churna and shilajit was measured on ethanol withdrawal anxiety using elevated plus maze. Role of ashwagandha and shilajit on chronic ethanol consumption (21 days) was measured using two bottle choice protocol of voluntary drinking. We also measured the effect of the above herbs on corticohippocampal GABA, dopamine, and serotonin levels. Both ashwagandha and shilajit were found to reduce alcohol withdrawal anxiety in a dose-dependent manner. These herbs alone or in combination also decreased ethanol intake and increased water intake significantly after 21 days of chronic administration. Chronic administration of ashwagandha was found to significantly increase GABA and serotonin levels whereas shilajit altered cortico-hippocampal dopamine in mice. These central nervous system active herbs alone or in combination reduced both alcohol dependence and withdrawal thus showing promising anti-addictive potential. Withinia Somnifera alone and in combination with Shilajeet prevented ethanol withdrawal and alcohol addiction Abbreviations used: GABA: Gama aminobutyric acid, CNS: Central Nervous System, CPP:Condition place preference, DA: Dopamine, 5-HT: 5-hydroxytryptamine, NMDA:N-methyl-D-aspartate.

  13. Parent's alcoholism severity and family topic avoidance about alcohol as predictors of perceived stigma among adult children of alcoholics: Implications for emotional and psychological resilience.

    PubMed

    Haverfield, Marie C; Theiss, Jennifer A

    2016-01-01

    Alcoholism is a highly stigmatized condition, with both alcohol-dependent individuals and family members of the afflicted experiencing stigmatization. This study examined the severity of a parent's alcoholism and family topic avoidance about alcohol as two factors that are associated with family members' perceptions of stigma. Three dimensions of stigma were considered: discrimination stigma, disclosure stigma, and positive aspect stigma. In addition, this study assessed associations between perceived stigmatization and individuals' experiences of depressive symptoms, self-esteem, and resilience. Adult children of alcoholics (N = 622) were surveyed about family conditions, perceived stigma, and their emotional and psychological well-being. Regression analyses revealed that the severity of a parent's alcoholism predicted all three types of stigma for females, but not for males. In addition, family topic avoidance about alcohol predicted all types of stigma for males and discrimination stigma and positive aspect stigma for females. With few exceptions, the three types of stigma predicted depressive symptoms, self-esteem, and resilience for both male and female adult children of alcoholics. The results are discussed in terms of their implications for promoting a family environment that mitigates stigma and encourages emotional and psychological well-being. In 2012, approximately 3.3 million deaths worldwide were due to the harmful use of alcohol (World Health Organization [WHO], 2014). Individuals who abuse alcohol are susceptible to a variety of negative health outcomes (Rehm et al., 2009) and display inappropriate social behaviors (Klingemann, 2001; Schomerus et al., 2011a). General societal perceptions tend to characterize alcohol-dependent individuals as irresponsible and lacking in self-control (Schomerus et al., 2011b). Research in the United Kingdom found that 54% of the population believes alcohol-dependent individuals are personally to blame for their own

  14. The effects of drug and alcohol consumption on driver injury severities in single-vehicle crashes.

    PubMed

    Behnood, Ali; Mannering, Fred L

    2017-07-04

    It is well known that alcohol and drugs influence driving behavior by affecting the central nervous system, awareness, vision, and perception/reaction times, but the resulting effect on driver injuries in car crashes is not fully understood. The purpose of this study was to identify factors affecting the injury severities of unimpaired, alcohol-impaired, and drug-impaired drivers. The current article applies a random parameters logit model to study the differences in injury severities among unimpaired, alcohol-impaired, and drug-impaired drivers. Using data from single-vehicle crashes in Cook County, Illinois, over a 9-year period from January 1, 2004, to December 31, 2012, separate models for unimpaired, alcohol-impaired, and drug-impaired drivers were estimated. A wide range of variables potentially affecting driver injury severity was considered, including roadway and environmental conditions, driver attributes, time and location of the crash, and crash-specific factors. The estimation results show significant differences in the determinants of driver injury severities across groups of unimpaired, alcohol-impaired, and drug-impaired drivers. The findings also show that unimpaired drivers are understandably more responsive to variations in lighting, adverse weather, and road conditions, but these drivers also tend to have much more heterogeneity in their behavioral responses to these conditions, relative to impaired drivers. In addition, age and gender were found to be important determinants of injury severity, but the effects varied significantly across all drivers, particularly among alcohol-impaired drivers. The model estimation results show that statistically significant differences exist in driver injury severities among the unimpaired, alcohol-impaired, and drug-impaired driver groups considered. Specifically, we find that unimpaired drivers tend to have more heterogeneity in their injury outcomes in the presence potentially adverse weather and road surface

  15. Acute illness-induced behavioral alterations are similar to those observed during withdrawal from acute alcohol exposure

    PubMed Central

    Richey, Laura; Doremus-Fitzwater, Tamara L.; Buck, Hollin M.; Deak, Terrence

    2012-01-01

    Exposure to an immunogen results in a constellation of behavioral changes collectively referred to as “sickness behaviors,” with alterations in cytokine expression previously shown to contribute to this sickness response. Since behaviors observed during ethanol withdrawal are strikingly similar to sickness behaviors, we hypothesized that behavioral manifestations of ethanol withdrawal might be an expression of sickness behaviors induced by ethanol-related changes in peripheral and/or central cytokine expression. Accordingly, behaviors exhibited during a modified social investigation test were first characterized in male rats following an acute injection of lipopolysaccharide (LPS; 100 μg/kg). Subsequently, behavioral changes after either a high (4-g/kg; Experiment 2) or low dose (0.5 g/kg; Experiment 3) of ethanol were also examined in the same social investigation test, as well as in the forced-swim test (FST; Experiment 4). Results from these experiments demonstrated similar reductions in both exploration and social investigatory behavior during acute illness and ethanol withdrawal, while a seemingly paradoxical decrease in immobility was observed in the FST during acute ethanol withdrawal. In follow-up studies, neither indomethacin (Experiment 5) nor interleukin-1 receptor antagonist (Experiment 6) pre-exposure reversed the ethanol withdrawal-induced behavioral changes observed in this social investigation test. Taken together, these studies demonstrate that the behavioral sequelae of acute illness and ethanol withdrawal are similar in nature, while antagonist studies suggest that these behavioral alterations are not reversed by blockade of IL-1 receptors or inhibition of prostaglandin synthesis. Though a direct mechanistic link between cytokines and the expression of acute ethanol withdrawal-related behaviors has yet to be found, future studies examining the involvement of brain cytokines as potential mediators of ethanol effects are greatly needed. PMID

  16. Blocking microglial pannexin-1 channels alleviates morphine withdrawal in rodents.

    PubMed

    Burma, Nicole E; Bonin, Robert P; Leduc-Pessah, Heather; Baimel, Corey; Cairncross, Zoe F; Mousseau, Michael; Shankara, Jhenkruthi Vijaya; Stemkowski, Patrick L; Baimoukhametova, Dinara; Bains, Jaideep S; Antle, Michael C; Zamponi, Gerald W; Cahill, Catherine M; Borgland, Stephanie L; De Koninck, Yves; Trang, Tuan

    2017-03-01

    Opiates are essential for treating pain, but termination of opiate therapy can cause a debilitating withdrawal syndrome in chronic users. To alleviate or avoid the aversive symptoms of withdrawal, many of these individuals continue to use opiates. Withdrawal is therefore a key determinant of opiate use in dependent individuals, yet its underlying mechanisms are poorly understood and effective therapies are lacking. Here, we identify the pannexin-1 (Panx1) channel as a therapeutic target in opiate withdrawal. We show that withdrawal from morphine induces long-term synaptic facilitation in lamina I and II neurons within the rodent spinal dorsal horn, a principal site of action for opiate analgesia. Genetic ablation of Panx1 in microglia abolished the spinal synaptic facilitation and ameliorated the sequelae of morphine withdrawal. Panx1 is unique in its permeability to molecules up to 1 kDa in size and its release of ATP. We show that Panx1 activation drives ATP release from microglia during morphine withdrawal and that degrading endogenous spinal ATP by administering apyrase produces a reduction in withdrawal behaviors. Conversely, we found that pharmacological inhibition of ATP breakdown exacerbates withdrawal. Treatment with a Panx1-blocking peptide ( 10 panx) or the clinically used broad-spectrum Panx1 blockers, mefloquine or probenecid, suppressed ATP release and reduced withdrawal severity. Our results demonstrate that Panx1-mediated ATP release from microglia is required for morphine withdrawal in rodents and that blocking Panx1 alleviates the severity of withdrawal without affecting opiate analgesia.

  17. What is the latent structure of alcohol use disorders? A taxometric analysis of the Personality Assessment Inventory Alcohol Problems Scale in male and female prison inmates.

    PubMed

    Walters, Glenn D; Diamond, Pamela M; Magaletta, Philip R

    2010-03-01

    Three indicators derived from the Personality Assessment Inventory (PAI) Alcohol Problems scale (ALC)-tolerance/high consumption, loss of control, and negative social and psychological consequences-were subjected to taxometric analysis-mean above minus below a cut (MAMBAC), maximum covariance (MAXCOV), and latent mode factor analysis (L-Mode)-in 1,374 federal prison inmates (905 males, 469 females). Whereas the total sample yielded ambiguous results, the male subsample produced dimensional results, and the female subsample produced taxonic results. Interpreting these findings in light of previous taxometric research on alcohol abuse and dependence it is speculated that while alcohol use disorders may be taxonic in female offenders, they are probably both taxonic and dimensional in male offenders. Two models of male alcohol use disorder in males are considered, one in which the diagnostic features are categorical and the severity of symptomatology is dimensional, and one in which some diagnostic features (e.g., withdrawal) are taxonic and other features (e.g., social problems) are dimensional.

  18. Increased startle potentiation to unpredictable stressors in alcohol dependence: Possible stress neuroadaptation in humans

    PubMed Central

    Moberg, Christine A.; Bradford, Daniel E.; Kaye, Jesse T.; Curtin, John J.

    2017-01-01

    Stress plays a key role in addiction etiology and relapse. Rodent models posit that following repeated periods of alcohol and other drug intoxication, compensatory allostatic changes occur in the central nervous system (CNS) circuits involved in behavioral and emotional response to stressors. We examine a predicted manifestation of this neuroadaptation in recently abstinent alcohol dependent humans. Participants completed a translational laboratory task that uses startle potentiation to unpredictable (vs. predictable) stressors implicated in the putative CNS mechanisms that mediate this neuroadaptation. Alcohol dependent participants displayed significantly greater startle potentiation to unpredictable than predictable stressors relative to non-alcoholic controls. The size of this effect covaried with alcohol-related problems and degree of withdrawal syndrome. This supports the rodent model thesis of a sensitized stress response in abstinent alcoholics. However, this effect could also represent pre-morbid risk or mark more severe and/or comorbid psychopathology. Regardless, pharmacotherapy and psychological interventions may target unpredictable stressor response to reduce stress-induced relapse. PMID:28394145

  19. Correlation between plasma homocysteine levels and craving in alcohol dependent stabilized patients.

    PubMed

    Coppola, Maurizio; Mondola, Raffaella

    2018-06-01

    Homocysteine is a sulfur amino acid strictly related with alcohol consumption. In alcoholics, hyperhomocysteinemia can increase the risk of various alcohol-related disorders such as: brain atrophy, epileptic seizures during withdrawal, and mood disorders. To evaluate the correlation among serum homocysteine concentrations, craving, hazardous and harmful patterns of alcohol consumption in patients stabilized for withdrawal symptoms. Participants were adult outpatients accessed at the Addiction Treatment Unit. Alcoholism was assessed using the following tools: Mini-International Neuropsychiatric Interview Plus (MINI Plus), Alcohol Use Disorder Identification test (AUDIT), Visual Analogic Scale for craving (VAS). Furthermore, during the first visit a blood sample was taken from all patients to measure the plasma concentration of both homocysteine and Carboxy Deficient Transferrin (CDT). Differences between groups in socio-demographic and clinical characteristics were analyzed using the t-test and the Mann-Whitney's U test for normally and non-normally distributed data, respectively. Correlation between clinical scale scores and plasma concentration of homocysteine and CDT was evaluated using the Pearson's correlation coefficient and the Kendall's Tau-b bivariate correlation coefficient for normally and non-normally distributed data, respectively. Our study included 92 patients. No difference was found in socio-demographic characteristics between groups. The group with high homocysteine had higher prevalence of mood disorders (p < 0.001), plasma CDT percentage (p < 0.001), VAS score (p < 0.001) and AUDIT score (p < 0.001) than group with normal homocysteine. Plasma homocysteine showed a positive correlation with both VAS score (p < 0.001), and AUDIT score (p < 0.05). In our study, plasma homocysteine concentration is associated with craving, hazardous and harmful patterns of alcohol consumption. In particular, homocysteine is correlated with alcoholism in a

  20. DSM-5 Alcohol Use Disorder Severity in Puerto Rico: Prevalence, Criteria Profile, and Correlates.

    PubMed

    Caetano, Raul; Gruenewald, Paul; Vaeth, Patrice A C; Canino, Glorisa

    2018-02-01

    Our aim was to examine lifetime criteria profiles and correlates of severity (mild, moderate, severe) of DSM-5 alcohol use disorders (AUD) in Puerto Rico. Data are from a household random sample of individuals 18 to 64 years of age in San Juan, Puerto Rico. The survey response rate was 83%. DSM-5 AUD was identified with the Spanish version of the World Health Organization's Composite International Diagnostic Interview. The analyses also identify correlates of each severity level using an ordered logistic regression model. The prevalence of lifetime DSM-5 AUD among men and women was 38 and 16%, respectively. Mild lifetime DSM-5 AUD was the most prevalent severity level among both men (18%) and women (9%). The most common criteria, independent of gender and severity level, were drinking larger quantities and for longer than planned (men range: 80 to 97%; women range: 78 to 91%) and hazardous use (men range: 56 to 91%; women range: 42 to 74%). Results from ordered logistic regression showed that the adjusted odds ratio for weekly drinking frequency, greater volume of alcohol consumed per drinking occasion, positive attitudes about drinking, drinking norms, and male gender invariantly increased risks across all DSM-5 AUD severity levels (mild, moderate, severe). Greater negative attitudes about drinking, low family cohesion, and Protestant religion were related to greater risks at higher AUD severity levels. AUD prevalence is high in San Juan, Puerto Rico. Prevalence rates for some criteria are equally high across severity levels and poorly differentiate between mild, moderate, or severe DSM-5 AUD. The sociodemographic and alcohol-related risks vary across DSM-5 severity levels. Copyright © 2018 by the Research Society on Alcoholism.

  1. Baclofen and Alcohol-Dependent Patients: A Real Risk of Severe Self-Poisoning.

    PubMed

    Boels, David; Victorri-Vigneau, Caroline; Grall-Bronnec, Marie; Touré, Ali; Garnier, Anais; Turcant, Alain; Le Roux, Gaël

    2017-10-01

    Baclofen is often prescribed in high doses to fight cravings experienced by alcohol-dependent patients. Such an increase in the availability of baclofen is concerning. This study aimed to determine the change in number and profile of self-poisoning with baclofen over time, as baclofen has become increasingly popular, in order to describe the severity of self-poisoning with baclofen and to focus on co-existing alcohol use disorders, and psychiatric illnesses determine predictors of severity. This was a retrospective study of self-poisoning with baclofen as reported by the western France Poison Control Center (PCC), which represents a population of more than 12 million people from January 2008 to March 2014. One hundred and eleven cases of self-poisoning with baclofen were reported to the western France PCC (62 males and 49 females; average age 39 ± 12). Poisoning severities were as follows: 'null' (nine cases), 'minor' (37 cases), 'moderate' (19 cases) and 'high' (46 cases, including four deaths). The most frequently reported symptoms were neurological (45%) and cardiovascular (27%). The severity was significantly associated with psychiatric disorders (OR = 2.9; p = 0.03). Baclofen, prescribed in high doses, may lead to severe poisoning, particularly in patients with psychiatric illnesses. Authorities should put forward a new policy for prescribing the drug as a treatment for alcohol dependence. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  2. Cocaine withdrawal

    MedlinePlus

    ... Substance use - cocaine withdrawal; Substance abuse - cocaine withdrawal; Drug abuse - cocaine withdrawal; Detox - cocaine ... Elsevier Saunders; 2016:chap 50. National Institute on Drug Abuse. What is cocaine? Updated May 2016. www.drugabuse. ...

  3. Family dysfunction differentially affects alcohol and methamphetamine dependence: a view from the Addiction Severity Index in Japan.

    PubMed

    Sugaya, Nagisa; Haraguchi, Ayako; Ogai, Yasukazu; Senoo, Eiichi; Higuchi, Susumu; Umeno, Mitsuru; Aikawa, Yuzo; Ikeda, Kazutaka

    2011-10-01

    We investigated the differential influence of family dysfunction on alcohol and methamphetamine dependence in Japan using the Addiction Severity Index (ASI), a useful instrument that multilaterally measures the severity of substance dependence. The participants in this study were 321 male patients with alcohol dependence and 68 male patients with methamphetamine dependence. We conducted semi-structured interviews with each patient using the ASI, which is designed to assess problem severity in seven functional domains: Medical, Employment/Support, Alcohol use, Drug use, Legal, Family/Social relationships, and Psychiatric. In patients with alcohol dependence, bad relationships with parents, brothers and sisters, and friends in their lives were related to current severe psychiatric problems. Bad relationships with brothers and sisters and partners in their lives were related to current severe employment/support problems, and bad relationships with partners in their lives were related to current severe family/social problems. The current severity of psychiatric problems was related to the current severity of drug use and family/social problems in patients with alcohol dependence. Patients with methamphetamine dependence had difficulty developing good relationships with their father. Furthermore, the current severity of psychiatric problems was related to the current severity of medical, employment/support, and family/social problems in patients with methamphetamine dependence. The results of this study suggest that family dysfunction differentially affects alcohol and methamphetamine dependence. Additionally, family relationships may be particularly related to psychiatric problems in these patients, although the ASI was developed to independently evaluate each of seven problem areas.

  4. Family Dysfunction Differentially Affects Alcohol and Methamphetamine Dependence: A View from the Addiction Severity Index in Japan

    PubMed Central

    Sugaya, Nagisa; Haraguchi, Ayako; Ogai, Yasukazu; Senoo, Eiichi; Higuchi, Susumu; Umeno, Mitsuru; Aikawa, Yuzo; Ikeda, Kazutaka

    2011-01-01

    We investigated the differential influence of family dysfunction on alcohol and methamphetamine dependence in Japan using the Addiction Severity Index (ASI), a useful instrument that multilaterally measures the severity of substance dependence. The participants in this study were 321 male patients with alcohol dependence and 68 male patients with methamphetamine dependence. We conducted semi-structured interviews with each patient using the ASI, which is designed to assess problem severity in seven functional domains: Medical, Employment/Support, Alcohol use, Drug use, Legal, Family/Social relationships, and Psychiatric. In patients with alcohol dependence, bad relationships with parents, brothers and sisters, and friends in their lives were related to current severe psychiatric problems. Bad relationships with brothers and sisters and partners in their lives were related to current severe employment/support problems, and bad relationships with partners in their lives were related to current severe family/social problems. The current severity of psychiatric problems was related to the current severity of drug use and family/social problems in patients with alcohol dependence. Patients with methamphetamine dependence had difficulty developing good relationships with their father. Furthermore, the current severity of psychiatric problems was related to the current severity of medical, employment/support, and family/social problems in patients with methamphetamine dependence. The results of this study suggest that family dysfunction differentially affects alcohol and methamphetamine dependence. Additionally, family relationships may be particularly related to psychiatric problems in these patients, although the ASI was developed to independently evaluate each of seven problem areas. PMID:22073020

  5. Effects of alcohol on the membrane excitability and synaptic transmission of medium spiny neurons in the nucleus accumbens

    PubMed Central

    Marty, Vincent N.; Spigelman, Igor

    2013-01-01

    Chronic and excessive alcohol drinking lead to alcohol dependence and loss of control over alcohol consumption, with serious detrimental health consequences. Chronic alcohol exposure followed by protracted withdrawal causes profound alterations in the brain reward system that leads to marked changes in reinforcement mechanisms and motivational state. These long-lasting neuroadaptations are thought to contribute to the development of cravings and relapse. The nucleus accumbens (NAcc), a central component of the brain reward system, plays a critical role in alcohol-induced neuroadaptive changes underlying alcohol-seeking behaviors. Here we review the findings that chronic alcohol exposure produces long-lasting neuroadaptive changes in various ion channels that govern intrinsic membrane properties and neuronal excitability, as well as excitatory and inhibitory synaptic transmission in the NAcc that underlie alcohol-seeking behavior during protracted withdrawal. PMID:22445807

  6. Effects of the mGluR2/3 agonist LY379268 and the mGluR5 antagonist MPEP on handling-induced convulsions during ethanol withdrawal in mice

    PubMed Central

    Olive, M. Foster; Becker, Howard C.

    2008-01-01

    In alcoholic patients, ethanol is often consumed in a repeated cyclic pattern of intoxication followed by abstinence and the emergence of withdrawal symptoms. Repeated cycles of ethanol intoxication and withdrawal lead to a sensitization of CNS hyperexcitability as a result of an imbalance between inhibitory GABAergic transmission and excitatory glutamatergic transmission. Symptoms of alcohol withdrawal are usually treated pharmacologically with either benzodiazepines or anticonvulsant medications. However, recent evidence suggests that inhibition of glutamate transmission by stimulation of presynaptic inhibitory metabotropic glutamate receptors (i.e., mGluR2/3 receptors) or inhibition of mGluR5 receptors produces anticonvulsant effects. Therefore, the present study was designed to determine the effects the mGluR2/3 agonist LY379268 and the mGluR5 antagonist MPEP on ethanol withdrawal-induced seizure activity. Adult male C3H/He mice received chronic 16 h of ethanol vapor exposure in inhalation chambers followed by 8 hr of withdrawal daily for 4 consecutive days. During the final (fourth) withdrawal cycle, mice were evaluated hourly for handling-induced convulsions (HIC), and were treated with vehicle, LY379268 (0.3, 1 and 3 mg/kg) or MPEP (1, 3 and 10 mg/kg) treatment at 4 and 8 hr into withdrawal. Significant reductions in overall HIC activity were not observed following administration of either compound. These results suggest that inhibition of glutamate transmission by mGluR2/3 agonists or mGluR5 antagonists does not alter HIC activity during withdrawal from repeated ethanol exposure, and as such these compounds may have limited usefulness in the treatment of CNS hyperexcitability during alcohol withdrawal. PMID:18420113

  7. AUDIT-C scores as a scaled marker of mean daily drinking, alcohol use disorder severity, and probability of alcohol dependence in a U.S. general population sample of drinkers.

    PubMed

    Rubinsky, Anna D; Dawson, Deborah A; Williams, Emily C; Kivlahan, Daniel R; Bradley, Katharine A

    2013-08-01

    Brief alcohol screening questionnaires are increasingly used to identify alcohol misuse in routine care, but clinicians also need to assess the level of consumption and the severity of misuse so that appropriate intervention can be offered. Information provided by a patient's alcohol screening score might provide a practical tool for assessing the level of consumption and severity of misuse. This post hoc analysis of data from the 2001 to 2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) included 26,546 U.S. adults who reported drinking in the past year and answered additional questions about their consumption, including Alcohol Use Disorders Identification Test-Consumption questionnaire (AUDIT-C) alcohol screening. Linear or logistic regression models and postestimation methods were used to estimate mean daily drinking, the number of endorsed alcohol use disorder (AUD) criteria ("AUD severity"), and the probability of alcohol dependence associated with each individual AUDIT-C score (1 to 12), after testing for effect modification by gender and age. Among eligible past-year drinkers, mean daily drinking, AUD severity, and the probability of alcohol dependence increased exponentially across increasing AUDIT-C scores. Mean daily drinking ranged from < 0.1 to 18.0 drinks/d, AUD severity ranged from < 0.1 to 5.1 endorsed AUD criteria, and probability of alcohol dependence ranged from < 1 to 65% across scores 1 to 12. AUD severity increased more steeply across AUDIT-C scores among women than men. Both AUD severity and mean daily drinking increased more steeply across AUDIT-C scores among younger versus older age groups. Results of this study could be used to estimate patient-specific consumption and severity based on age, gender, and alcohol screening score. This information could be integrated into electronic decision support systems to help providers estimate and provide feedback about patient-specific risks and identify those patients most

  8. Molecular basis of alcoholism.

    PubMed

    Most, Dana; Ferguson, Laura; Harris, R Adron

    2014-01-01

    Acute alcohol intoxication causes cellular changes in the brain that last for hours, while chronic alcohol use induces widespread neuroadaptations in the nervous system that can last a lifetime. Chronic alcohol use and the progression into dependence involve the remodeling of synapses caused by changes in gene expression produced by alcohol. The progression of alcohol use, abuse, and dependence can be divided into stages, which include intoxication, withdrawal, and craving. Each stage is associated with specific changes in gene expression, cellular function, brain circuits, and ultimately behavior. What are the molecular mechanisms underlying the transition from recreational use (acute) to dependence (chronic)? What cellular adaptations result in drug memory retention, leading to the persistence of addictive behaviors, even after prolonged drug abstinence? Research into the neurobiology of alcoholism aims to answer these questions. This chapter will describe the molecular adaptations caused by alcohol use and dependence, and will outline key neurochemical participants in alcoholism at the molecular level, which are also potential targets for therapy. © 2014 Elsevier B.V. All rights reserved.

  9. GABAB receptor ligands for the treatment of alcohol use disorder: preclinical and clinical evidence

    PubMed Central

    Agabio, Roberta; Colombo, Giancarlo

    2014-01-01

    The present paper summarizes the preclinical and clinical studies conducted to define the “anti-alcohol” pharmacological profile of the prototypic GABAB receptor agonist, baclofen, and its therapeutic potential for treatment of alcohol use disorder (AUD). Numerous studies have reported baclofen-induced suppression of alcohol drinking (including relapse- and binge-like drinking) and alcohol reinforcing, motivational, stimulating, and rewarding properties in rodents and monkeys. The majority of clinical surveys conducted to date—including case reports, retrospective chart reviews, and randomized placebo-controlled studies—suggest the ability of baclofen to suppress alcohol consumption, craving for alcohol, and alcohol withdrawal symptomatology in alcohol-dependent patients. The recent identification of a positive allosteric modulatory binding site, together with the synthesis of in vivo effective ligands, represents a novel, and likely more favorable, option for pharmacological manipulations of the GABAB receptor. Accordingly, data collected to date suggest that positive allosteric modulators of the GABAB receptor reproduce several “anti-alcohol” effects of baclofen and display a higher therapeutic index (with larger separation—in terms of doses—between “anti-alcohol” effects and sedation). PMID:24936171

  10. 78 FR 39256 - Polyvinyl Alcohol From Taiwan: Rescission of Antidumping Duty Administrative Review; 2012-2013

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-01

    ... DEPARTMENT OF COMMERCE International Trade Administration [A-583-841] Polyvinyl Alcohol From...) is rescinding its administrative review of the antidumping duty order on polyvinyl alcohol (PVA) from... CCPC to the Department, ``Polyvinyl Alcohol from Taiwan: Withdrawal of Administrative Review Request...

  11. Efficacy of transcranial magnetotherapy in the complex treatment of alcohol withdrawal syndrome.

    PubMed

    Staroverov, A T; Zhukov, O B; Raigorodskii, Yu M

    2009-11-01

    A total of 54 patients with alcoholism were studied during abstinence. Of these, 29 patients in the experimental group received basal therapy supplemented with physical treatment consisting of transcranial dynamic magnetotherapy (TcDMT), while the control group of 25 patients received only basal therapy. Comparison of the status of patients in the experimental and control groups during treatment demonstrated advantages of TcDMT in relation to improving the functional state of the CNS, memory, and attention, the autonomic nervous system, and the psychoemotional status of the patients (with decreases in the severity of anxiety and depression).

  12. Perceived barriers to quitting smoking among alcohol dependent patients in treatment.

    PubMed

    Asher, Marilyn K; Martin, Rosemarie A; Rohsenow, Damaris J; MacKinnon, Selene Varney; Traficante, Regina; Monti, Peter M

    2003-03-01

    Little is known about the perceived barriers to quitting smoking among alcohol abusers. In addition to the usual barriers perceived by smokers, alcohol dependent smokers may have a few barriers unique to their addictive lifestyle. The Barriers to Quitting Smoking in Substance Abuse Treatment (BQS-SAT) was administered to 96 alcohol dependent smokers in residential substance abuse treatment. The BQS-SAT is designed to assess perceived barriers to quitting smoking among alcohol abusers using eleven true-false items. One open-ended item was included to gather information about potential additional barriers. The majority of respondents reported withdrawal-related barriers such as expecting to feel irritable, anxious, restless, and about half expected intolerable urges to smoke if they were to quit smoking, as most smokers do. However, concerns about effects on sobriety and needing cigarettes to cope with feeling down were also endorsed by almost half of the patients. Total number of perceived barriers was significantly related to smoking history, expected effects from smoking, and smoking temptation but was not associated with severity of alcohol use or dependence on admission. Providing corrective feedback about these barriers could be useful when addressing smoking with patients who have alcohol abuse or dependence.

  13. Withdrawal

    MedlinePlus

    ... However, withdrawal is considered a better method of contraception than none at all. Protection Against STDs Withdrawal ... 2013 More on this topic for: Teens Emergency Contraception Talking to Your Partner About Condoms Birth Control ...

  14. Alcohol use by alcoholics with and without a history of parental alcoholism.

    PubMed

    Worobec, T G; Turner, W M; O'Farrell, T J; Cutter, H S; Bayog, R D; Tsuang, M T

    1990-12-01

    The association between parental history of alcoholism and the nature of alcoholism was assessed using a more reliable measure of family history (Family Tree Questionnaire) and a more comprehensive inventory of alcoholism (Alcohol Use Inventory) than used in earlier studies. Parental alcoholism was associated with more severe alcoholism on most parameters of alcohol use (age of onset, quantity, frequency, preoccupation, and sustained use) and alcohol-related problems (social, vocational, physical, cognitive, and loss of control). The association between parental history of alcoholism and more severe alcoholism in the probands was independent of age of onset of alcoholism, current age, socioeconomic background, and marital status. Parental history positive (PH+) alcoholics were more reliant on alcohol to manage their moods but did not differ significantly from parental history negative (PH-) alcoholics in the use of alcohol to improve sociability or mental functioning or to cope with marital problems. Surprisingly, the degree of concern, guilt, and worry over the negative consequences of drinking was not significantly different for PH+ alcoholics although the negative consequences were clearly much more severe for this group. While the data are inconclusive about the reasons for more severe alcoholism in PH+ alcoholics, greater reliance on ethanol to manage moods and a relative insensitivity to negative consequences could theoretically account for the vulnerability to more severe alcoholism found in PH+ alcoholics.

  15. Sex Differences in Ethanol's Anxiolytic Effect and Chronic Ethanol Withdrawal Severity in Mice with a Null Mutation of the 5α-Reductase Type 1 Gene.

    PubMed

    Tanchuck-Nipper, Michelle A; Ford, Matthew M; Hertzberg, Anna; Beadles-Bohling, Amy; Cozzoli, Debra K; Finn, Deborah A

    2015-05-01

    Manipulation of endogenous levels of the GABAergic neurosteroid allopregnanolone alters sensitivity to some effects of ethanol. Chronic ethanol withdrawal decreases activity and expression of 5α-reductase-1, an important enzyme in allopregnanolone biosynthesis encoded by the 5α-reductase-1 gene (Srd5a1). The present studies examined the impact of Srd5a1 deletion in male and female mice on several acute effects of ethanol and on chronic ethanol withdrawal severity. Genotype and sex did not differentially alter ethanol-induced hypothermia, ataxia, hypnosis, or metabolism, but ethanol withdrawal was significantly lower in female versus male mice. On the elevated plus maze, deletion of the Srd5a1 gene significantly decreased ethanol's effect on total entries versus wildtype (WT) mice and significantly decreased ethanol's anxiolytic effect in female knockout (KO) versus WT mice. The limited sex differences in the ability of Srd5a1 genotype to modulate select ethanol effects may reflect an interaction between developmental compensations to deletion of the Srd5a1 gene with sex hormones and levels of endogenous neurosteroids.

  16. Socially anxious smokers experience greater negative affect and withdrawal during self-quit attempts.

    PubMed

    Buckner, Julia D; Langdon, Kirsten J; Jeffries, Emily R; Zvolensky, Michael J

    2016-04-01

    Despite evidence of a strong and consistent relation between smoking and elevated social anxiety, strikingly little empirical work has identified mechanisms underlying the smoking-social anxiety link. Persons with elevated social anxiety may rely on smoking to cope with more severe nicotine withdrawal and post-quit negative mood states; yet, no known studies have investigated the relation of social anxiety to withdrawal severity. The current study examined the relation of social anxiety to post-quit nicotine withdrawal severity among 51 (33.3% female, Mage = 34.6) community-recruited smokers during the first two weeks following an unaided (i.e., no treatment) cessation attempt. Ecological momentary assessment was used to collect multiple daily ratings of withdrawal and negative mood states. Baseline social anxiety was related to increases in negative affect during the monitoring period and remained significantly related to post-quit withdrawal after controlling for negative affect, gender, lapses, and substance use. Persons with elevated social anxiety experience more severe post-quit withdrawal symptoms and increases in negative affect during a cessation attempt and may therefore benefit from intervention and treatment strategies geared toward helping them learn to cope with withdrawal and negative affect to improve cessation rates among these vulnerable smokers.

  17. Refeeding syndrome is uncommon in alcoholics admitted to a hospital detoxification unit.

    PubMed

    Manning, S; Gilmour, M; Weatherall, M; Robinson, G M

    2014-05-01

    The refeeding syndrome is increasingly recognised. It is a serious change in electrolytes when nutrition is reintroduced to malnourished patients. Alcohol dependence is a risk factor for the refeeding syndrome. We report a prospective cohort study of 36 alcoholics hospitalised for withdrawal management. We found no evidence of refeeding syndrome in any patient after 3 days of hospitalisation, despite hypomagnesaemia, a risk factor for the refeeding syndrome being prevalent (44% of subjects). Low thiamine levels were infrequent affecting 3/29 (10%). We recommend that in alcoholics admitted for managed withdrawal, risk of refeeding syndrome appears to be low, and routine testing of repeat electrolytes appears unnecessary. © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

  18. Control of ethanol withdrawal symptoms in mice by phenytoin.

    PubMed

    Sprague, G L; Craigmill, A L

    1976-12-01

    Mice were made physically dependent upon ethanol using either of two methods which involved ethanol vapor inhalation. Following the cessation of exposure to ethanol, the severity of handling-induced convulsions and changes in the response to an electric foot shock (startle reflex) were recorded. Animals given isotonic saline or propylene glycol:ethanol vehicle during withdrawal exhibited handling-induced convulsions, and ethanol (2.0-4.0 g/kg) or phenytoin (5-20 mg/kg) administration during withdrawal resulted in a reduction in the severity of these convulsions. A reduced startle reflex threshold was also evident during withdrawal in mice given isotonic saline or propylene glycol:ethanol vehicle. Ethanol (0.5-4.0 g/kg) or phenytoin (10-20 mg/kg) administration during withdrawal resulted in a significant elevation of the startle reflex threshold compared to control animals. The results are discussed as they relate to others obtained in experimental and clinical studies.

  19. Alcohol consumption in late adolescence is associated with an increased risk of severe liver disease later in life.

    PubMed

    Hagström, Hannes; Hemmingsson, Tomas; Discacciati, Andrea; Andreasson, Anna

    2018-03-01

    High alcohol consumption is associated with an increased risk of severe liver disease. Current recommendations suggest it is safe for men to consume 30 grams of alcohol per day. We investigated the association between alcohol consumption early in life and later development of severe liver disease. We used data on alcohol consumption at conscription to military service from 43,296 men (18-20 years) in Sweden between 1969 and 1970. Outcomes were defined as incident diagnoses of severe liver disease from systematic national registration of clinical events until the end of 2009. A Cox regression model adjusted for body mass index, smoking, use of narcotics, cognitive ability and cardiovascular capacity was applied. During a mean follow-up of 37.8 years, 383 men developed severe liver disease. Alcohol consumption was associated with an increased risk of development of severe liver disease in a dose-response pattern (adjusted hazard ratio for every one gram/day increase 1.02; 95% CI 1.01-1.02). No evidence of a threshold effect was found. Importantly, a clear trend pointed towards an increased risk of severe liver disease in men who consumed less than 30 grams of alcohol per day. Alcohol consumption in young men is associated with an increased risk of severe liver disease, up to 39 years later in life. The risk was dose-dependent, with no sign of a threshold effect. Current guidelines for safe alcohol intake in men might have to be revised. We investigated more than 43,000 Swedish men in their late teens enlisted for conscription in 1969-1970. After almost 40 years of follow-up, we found that alcohol consumption was a significant risk factor for developing severe liver disease, independent of confounders. This risk was dose-dependent, and was most pronounced in men consuming two drinks per day or more. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  20. Differentiating Adolescent Suicide Attempters from Ideators: Examining the Interaction between Depression Severity and Alcohol Use

    PubMed Central

    McManama O’Brien, Kimberly H.; Becker, Sara J.; Spirito, Anthony; Simon, Valerie; Prinstein, Mitchell J.

    2014-01-01

    This study examined whether depressed mood, frequency of alcohol use, and their combination differentiated non-suicidal adolescents from those with suicidal ideation and adolescents with suicidal ideation from those who have made a suicide attempt. Hierarchical logistic regressions indicated that frequency of alcohol use did not differentiate non-suicidal adolescents from those with current suicidal ideation, but severity of depressed mood did so. In contrast, alcohol use was a significant differentiating factor between adolescents who had attempted suicide compared to those with suicidal ideation only, with severity of depressed mood not being significant. However, there was also a significant interaction effect such that for adolescents with suicidal ideation and low levels of depression, increased frequency of alcohol use was associated with increased odds of a suicide attempt. These findings suggest that alcohol use may hasten the transition from suicidal ideation to suicide attempt in adolescents with low levels of depressed mood. PMID:23889515

  1. Sex differences in cannabis withdrawal symptoms among treatment-seeking cannabis users

    PubMed Central

    Herrmann, Evan S.; Weerts, Elise M.; Vandrey, Ryan

    2015-01-01

    Over 300,000 individuals enter treatment for cannabis use disorders (CUDs) in the U.S. annually. Cannabis withdrawal is associated with poor CUD treatment outcomes, but no prior studies have examined sex differences in withdrawal among treatment-seeking cannabis users. Treatment-seeking cannabis users (45 women and 91 men) completed a Marijuana Withdrawal Checklist (MWC) at treatment intake to retrospectively characterize withdrawal symptoms experienced during their most recent quit attempt. Composite Withdrawal Discomfort Scale (WDS) scores were calculated using the 14 items on the MWC that correspond to valid cannabis withdrawal symptoms described in DSM-5. Demographic and substance use characteristics, overall WDS scores, and scores on individual WDS symptoms were compared between women and men. Women had higher overall WDS scores than men, and women had higher scores than men on six individual symptoms in two domains, mood symptoms (irritability, restlessness, increased anger, violent outbursts) and gastrointestinal symptoms (nausea, stomach pain). Follow-up analyses isolating the incidence and severity of WDS symptoms demonstrated that women generally reported a higher number of individual withdrawal symptoms than men, and that they reported experiencing some symptoms as more severe. This is the first report to demonstrate that women seeking treatment for CUDs may experience more withdrawal then men during quit attempts. Prospective studies of sex differences in cannabis withdrawal are warranted. PMID:26461168

  2. Phenomenology of gasoline intoxication and withdrawal symptoms among adolescents in India: a case series.

    PubMed

    Shah, R; Vankar, G K; Upadhyaya, H P

    1999-01-01

    Inhalant withdrawal symptoms have previously been described but not well documented. This case-series describes the sociodemographic and clinical characteristics of nine children and adolescents with gasoline abuse. Gasoline inhalation was the drug of choice in our patients. The mean age was 13.6 years and all the subjects belonged to low socioeconomic status. Most of the subjects used daily and all subjects reported alcohol abuse in the father. All subjects reported a syndrome of intoxication as described in previous reports. All subjects also reported a withdrawal syndrome including irritability, psychomotor retardation, anhedonia, dry mouth, sleep disturbances, craving, and increased lacrimation.

  3. Grand Rounds: Alcoholic Hepatitis.

    PubMed

    Singal, Ashwani K; Louvet, Alexandre; Shah, Vijay H; Kamath, Patrick S

    2018-06-13

    A 33-year-old Caucasian male was admitted to hospital with recent onset of jaundice of 2-3 weeks duration. He reported heavy use of alcohol for the last 10 years with the last drink a day prior to the onset of symptoms. At admission, he was alert and oriented to time, place, and person, and was deeply jaundiced. His laboratory profile can be summarised as follows: haemoglobin 12.1 g/dl, white blood cell count 18,700 with 81% neutrophils, serum bilirubin 33 (direct 22) mg/dl, aspartate aminotransferase 147 IU/L, alanine aminotransferase 62 IU/L, alkaline phosphatase 117 IU/L, serum albumin 2.8 gm/dl, serum creatinine 0.6 mg/dl, prothrombin time 18.3 (control 14.5) seconds, and international normalized ratio 1.48. He was diagnosed with severe alcoholic hepatitis (Maddrey discriminant function score of 50) and treated with prednisolone for 28 days with symptomatic and biochemical improvement. His Lille score at seven days was 0.4, and his serum bilirubin had decreased to 3.5 mg/dl at the end of treatment. He was also seen by the addiction team during hospitalisation; he agreed to follow through on recommendations. He was dismissed after completing a three-week inpatient rehabilitation programme but relapsed to alcohol use three months later, and was readmitted with alcohol withdrawal. He was readmitted two months later (about six months from the first episode) for a second episode of severe alcoholic hepatitis. At admission, his model for end-stage liver disease score was 32 and he was treated again with corticosteroids. His Lille score at seven days was 0.6 and steroids were discontinued. The hospital course was complicated by spontaneous bacterial peritonitis and pneumonia with development of acute kidney injury. He continued to worsen, developing multiorgan failure. After a course of one month, the family's preference was for him to receive comfort measures. This scenario raises several questions. Copyright © 2018 European Association for the

  4. Healthy donor faecal transplant for corticosteroid non-responsive severe alcoholic hepatitis.

    PubMed

    Philips, Cyriac Abby; Phadke, Nikhil; Ganesan, Karthik; Augustine, Philip

    2017-11-08

    Patients with severe alcoholic hepatitis (SAH) have high mortality in the presence of steroid unresponsiveness in the absence of clear treatment recommendations. Liver transplantation is the curative option in such cases but is controversial in the wake of severe infections, post-transplant recidivism and long waiting on deceased donor listing. Animal and human studies have shed light on the beneficial effects of gut microbiota modulation in alcoholic liver disease. We present the first report of faecal microbiota transplantation (FMT) in a steroid non-responder in whom, clinical, biochemical and liver disease severity scores improved post-FMT and demonstrate distinct bacterial population changes pre-FMT and post-FMT. Healthy donor FMT could be safe and efficacious in SAH not responding to corticosteroid treatment, as a bridge to liver transplantation (LT) or in candidates who are unwilling or not ideal for LT for improvement in short-term transplant free survival. Larger controlled studies are required for confirmation. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  5. The FKBP5 Gene Affects Alcohol Drinking in Knockout Mice and Is Implicated in Alcohol Drinking in Humans.

    PubMed

    Qiu, Bin; Luczak, Susan E; Wall, Tamara L; Kirchhoff, Aaron M; Xu, Yuxue; Eng, Mimy Y; Stewart, Robert B; Shou, Weinian; Boehm, Stephen L; Chester, Julia A; Yong, Weidong; Liang, Tiebing

    2016-08-05

    FKBP5 encodes FK506-binding protein 5, a glucocorticoid receptor (GR)-binding protein implicated in various psychiatric disorders and alcohol withdrawal severity. The purpose of this study is to characterize alcohol preference and related phenotypes in Fkbp5 knockout (KO) mice and to examine the role of FKBP5 in human alcohol consumption. The following experiments were performed to characterize Fkpb5 KO mice. (1) Fkbp5 KO and wild-type (WT) EtOH consumption was tested using a two-bottle choice paradigm; (2) The EtOH elimination rate was measured after intraperitoneal (IP) injection of 2.0 g/kg EtOH; (3) Blood alcohol concentration (BAC) was measured after 3 h limited access of alcohol; (4) Brain region expression of Fkbp5 was identified using LacZ staining; (5) Baseline corticosterone (CORT) was assessed. Additionally, two SNPs, rs1360780 (C/T) and rs3800373 (T/G), were selected to study the association of FKBP5 with alcohol consumption in humans. Participants were college students (n = 1162) from 21-26 years of age with Chinese, Korean or Caucasian ethnicity. The results, compared to WT mice, for KO mice exhibited an increase in alcohol consumption that was not due to differences in taste sensitivity or alcohol metabolism. Higher BAC was found in KO mice after 3 h of EtOH access. Fkbp5 was highly expressed in brain regions involved in the regulation of the stress response, such as the hippocampus, amygdala, dorsal raphe and locus coeruleus. Both genotypes exhibited similar basal levels of plasma corticosterone (CORT). Finally, single nucleotide polymorphisms (SNPs) in FKBP5 were found to be associated with alcohol drinking in humans. These results suggest that the association between FKBP5 and alcohol consumption is conserved in both mice and humans.

  6. Sex differences in cannabis withdrawal symptoms among treatment-seeking cannabis users.

    PubMed

    Herrmann, Evan S; Weerts, Elise M; Vandrey, Ryan

    2015-12-01

    Over 300,000 individuals enter treatment for cannabis-use disorders (CUDs) in the United States annually. Cannabis withdrawal is associated with poor CUD-treatment outcomes, but no prior studies have examined sex differences in withdrawal among treatment-seeking cannabis users. Treatment-seeking cannabis users (45 women and 91 men) completed a Marijuana Withdrawal Checklist (Budney, Novy, & Hughes, 1999, Budney, Moore, Vandrey, & Hughes, 2003) at treatment intake to retrospectively characterize withdrawal symptoms experienced during their most recent quit attempt. Scores from the 14-item Composite Withdrawal Discomfort Scale (WDS), a subset of the Marijuana Withdrawal Checklist that corresponds to valid cannabis withdrawal symptoms described in the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; APA, 2013) were calculated. Demographic and substance-use characteristics, overall WDS scores, and scores on individual WDS symptoms were compared between women and men. Women had higher overall WDS scores than men, and women had higher scores than men on 6 individual symptoms in 2 domains, mood symptoms (i.e., irritability, restlessness, increased anger, violent outbursts), and gastrointestinal symptoms (i.e., nausea, stomach pain). Follow-up analyses isolating the incidence and severity of WDS symptoms demonstrated that women generally reported a higher number of individual withdrawal symptoms than men, and that they reported experiencing some symptoms as more severe. This is the first report to demonstrate that women seeking treatment for CUDs may experience more withdrawal then men during quit attempts. Prospective studies of sex differences in cannabis withdrawal are warranted. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  7. Sex Differences in Ethanol’s Anxiolytic Effect and Chronic Ethanol Withdrawal Severity in Mice With a Null Mutation of the 5α-Reductase Type 1 Gene

    PubMed Central

    Tanchuck-Nipper, Michelle A.; Ford, Matthew M.; Hertzberg, Anna; Beadles-Bohling, Amy; Cozzoli, Debra K.; Finn, Deborah A.

    2015-01-01

    Manipulation of endogenous levels of the GABAergic neurosteroid allopregnanolone alters sensitivity to some effects of ethanol. Chronic ethanol withdrawal decreases activity and expression of 5α-reductase-1, an important enzyme in allopregnanolone biosynthesis encoded by the 5α-reductase-1 gene (Srd5a1). The present studies examined the impact of Srd5a1 deletion in male and female mice on several acute effects of ethanol and on chronic ethanol withdrawal severity. Genotype and sex did not differentially alter ethanol-induced hypothermia, ataxia, hypnosis, or metabolism, but ethanol withdrawal was significantly lower in female versus male mice. On the elevated plus maze, deletion of the Srd5a1 gene significantly decreased ethanol’s effect on total entries versus wildtype (WT) mice and significantly decreased ethanol’s anxiolytic effect in female knockout (KO) versus WT mice. The limited sex differences in the ability of Srd5a1 genotype to modulate select ethanol effects may reflect an interaction between developmental compensations to deletion of the Srd5a1 gene with sex hormones and levels of endogenous neurosteroids. PMID:25355320

  8. Evaluation of the Anxiolytic Activity of NR-ANX-C (a Polyherbal Formulation) in Ethanol Withdrawal-Induced Anxiety Behavior in Rats.

    PubMed

    Mohan, L; Rao, U S C; Gopalakrishna, H N; Nair, V

    2011-01-01

    The present study investigates the anxiolytic activity of NR-ANX-C, a standardized polyherbal formulation containing the extracts of Withania somnifera, Ocimum sanctum, Camellia sinensis, Triphala, and Shilajit in ethanol withdrawal- (EW-) induced anxiety behavior in rats. Ethanol dependence in rats was produced by substitution of drinking water with 7.5% v/v alcohol for 10 days. Then, ethanol withdrawal was induced by replacing alcohol with drinking water, 12 hours prior to experimentation. After confirming induction of withdrawal symptoms in the alcohol deprived animals, the anxiolytic activity of the test compound in graded doses (10, 20, and 40 mg/kg) was compared to the standard drug alprazolam (0.08 mg/kg) in the elevated plus maze and bright and dark arena paradigms. In our study, single and repeated dose administration of NR-ANX-C reduced EW-induced anxiety in a dose-dependent manner. Even though the anxiolytic activity was not significant at lower doses, NR-ANX-C at the highest dose tested (40 mg/kg) produced significant anxiolytic activity that was comparable to the standard drug alprazolam. Based on our findings we believe that NR-ANX-C has the potential to be used as an alternative to benzodiazepines in the treatment of EW-induced anxiety.

  9. Evaluation of the Anxiolytic Activity of NR-ANX-C (a Polyherbal Formulation) in Ethanol Withdrawal-Induced Anxiety Behavior in Rats

    PubMed Central

    Mohan, L.; Rao, U. S. C.; Gopalakrishna, H. N.; Nair, V.

    2011-01-01

    The present study investigates the anxiolytic activity of NR-ANX-C, a standardized polyherbal formulation containing the extracts of Withania somnifera, Ocimum sanctum, Camellia sinensis, Triphala, and Shilajit in ethanol withdrawal- (EW-) induced anxiety behavior in rats. Ethanol dependence in rats was produced by substitution of drinking water with 7.5% v/v alcohol for 10 days. Then, ethanol withdrawal was induced by replacing alcohol with drinking water, 12 hours prior to experimentation. After confirming induction of withdrawal symptoms in the alcohol deprived animals, the anxiolytic activity of the test compound in graded doses (10, 20, and 40 mg/kg) was compared to the standard drug alprazolam (0.08 mg/kg) in the elevated plus maze and bright and dark arena paradigms. In our study, single and repeated dose administration of NR-ANX-C reduced EW-induced anxiety in a dose-dependent manner. Even though the anxiolytic activity was not significant at lower doses, NR-ANX-C at the highest dose tested (40 mg/kg) produced significant anxiolytic activity that was comparable to the standard drug alprazolam. Based on our findings we believe that NR-ANX-C has the potential to be used as an alternative to benzodiazepines in the treatment of EW-induced anxiety. PMID:20953426

  10. Nicotine and Nicotine Abstinence Do Not Interfere with GABAA Receptor Neuroadaptations During Alcohol Abstinence.

    PubMed

    Hillmer, Ansel T; Kloczynski, Tracy; Sandiego, Christine M; Pittman, Brian; Anderson, Jon M; Labaree, David; Gao, Hong; Huang, Yiyun; Deluliis, Giuseppe; O'Malley, Stephanie S; Carson, Richard E; Cosgrove, Kelly P

    2016-04-01

    Alcohol dependence and tobacco smoking are highly comorbid, and treating both conditions simultaneously is controversial. Previously, we showed that tobacco smoking interferes with GABAA receptor neuroadaptations during alcohol withdrawal in humans, while this effect did not occur with continued nicotine use during alcohol abstinence in nonhuman primates. Here, we extend our previous work by measuring GABAA receptor availability with positron emission tomography (PET) during drug abstinence in nonhuman primates exposed to alcohol alone, nicotine and alcohol together, and alcohol abstinence with continued nicotine exposure. Twenty-four adolescent male rhesus macaques orally self-administered alcohol and nicotine, available separately in water and saccharin, over 20 weeks. The groups included alcohol alone (n = 8); nicotine and alcohol with simultaneous abstinence (n = 8); nicotine and alcohol with alcohol abstinence while nicotine was still available (n = 8); and a pilot group of animals consuming nicotine alone (n = 6). Animals were imaged with [(11)C]flumazenil PET to measure binding potential (BPND), an index of GABAA receptor availability. Imaging occurred at baseline (drug-naíve), and following alcohol and/or nicotine cessation at 1 day, 8 days, and 12 weeks of abstinence. Generalized linear mixed models were used to examine the time course of [(11)C]flumazenil BPND during alcohol abstinence across groups. Animals consumed 3.95 ± 1.22 g/kg/d alcohol and 55.4 ± 35.1 mg/kg/d nicotine. No significant group effects were observed in [(11)C]flumazenil BPND during alcohol abstinence; however, a main effect of time was detected. Post hoc analyses indicated that all groups abstaining from alcohol exhibited significantly increased GABAA receptor availability at 1 day and 8 days (but not 12 weeks) of abstinence relative to baseline, while no changes in [(11)C]flumazenil BPND during nicotine abstinence alone were observed. These data indicate that neither nicotine nor

  11. CHRONIC ALCOHOL NEUROADAPTATION AND STRESS CONTRIBUTE TO SUSCEPTIBILITY FOR ALCOHOL CRAVING AND RELAPSE

    PubMed Central

    BREESE, GEORGE R.; SINHA, RAJITA; HEILIG, MARKUS

    2010-01-01

    Alcoholism is a chronic relapsing disorder. Major characteristics observed in alcoholics during an initial period of alcohol abstinence are altered physiological functions and a negative emotional state. Evidence suggests that a persistent, cumulative adaptation involving a kindling/allostasis-like process occurs during the course of repeated chronic alcohol exposures that is critical for the negative symptoms observed during alcohol withdrawal. Basic studies have provided evidence for specific neurotransmitters within identified brain sites being responsible for the negative emotion induced by the persistent cumulative adaptation following intermittent-alcohol exposures. After an extended period of abstinence, the cumulative alcohol adaptation increases susceptibility to stress- and alcohol cue-induced negative symptoms and alcohol seeking, both of which can facilitate excessive ingestion of alcohol. In the alcoholic, stressful imagery and alcohol cues alter physiological responses, enhance negative emotion, and induce craving. Brain fMRI imaging following stress and alcohol cues has documented neural changes in specific brain regions of alcoholics not observed in social drinkers. Such altered activity in brain of abstinent alcoholics to stress and alcohol cues is consistent with a continuing ethanol adaptation being responsible. Therapies in alcoholics found to block responses to stress and alcohol cues would presumably be potential treatments by which susceptibility for continued alcohol abuse can be reduced. By continuing to define the neurobiological basis of the sustained alcohol adaptation critical for the increased susceptibility of alcoholics to stress and alcohol cues that facilitate craving, a new era is expected to evolve in which the high rate of relapse in alcoholism is minimized. 250 PMID:20951730

  12. Urine ethanol concentration and alcohol hangover severity.

    PubMed

    Van de Loo, Aurora; Mackus, Marlou; Korte-Bouws, Gerdien; Brookhuis, Karel; Garssen, Johan; Verster, Joris

    2017-01-01

    The aim of this study was to examine the relationship between urine ethanol concentration and alcohol hangover severity. N = 36 healthy social drinkers participated in a naturalistic study, comprising a hangover day and a control day. N = 18 of them have regular hangovers (the hangover group), while the other N = 18 claim to be hangover immune (hangover-immune group). On each test day at 9.30 am, urine samples were collected. Participants rated their overall hangover severity on a scale from 0 (absent) to 10 (extreme), as well as 18 individual hangover symptoms. Urine ethanol concentration was significantly higher on the hangover day when compared to the control day (p = 0.006). On the hangover day, urine ethanol concentration was significantly lower in the hangover-immune group when compared to the hangover group (p = 0.027). In the hangover-immune group, none of the correlations of urine ethanol concentration with individual hangover symptoms was significant. In contrast, in the hangover group, significant correlations were found with a variety of hangover symptoms, including nausea, concentration problems, sleepiness, weakness, apathy, sweating, stomach pain, thirst, heart racing, anxiety, and sleep problems. Urine ethanol levels are significantly associated with the presence and severity of several hangover symptoms.

  13. Increased ethane exhalation, an in vivo index of lipid peroxidation, in alcohol-abusers.

    PubMed Central

    Lettéron, P; Duchatelle, V; Berson, A; Fromenty, B; Fisch, C; Degott, C; Benhamou, J P; Pessayre, D

    1993-01-01

    Ethane exhalation was measured in 42 control subjects, 52 patients with various non-alcoholic liver diseases, and 89 alcohol abusers who had been admitted to hospital for alcohol withdrawal and assessment of liver disease (six with normal liver tests, 10 with steatosis with or without fibrosis, six with alcoholic hepatitis, 29 with cirrhosis, 34 with both cirrhosis and alcoholic hepatitis, and four with both cirrhosis and a hepatocellular carcinoma). Ethane exhalation was similar in control subjects and in patients with non-alcoholic liver diseases, but was five times higher in alcohol abusers. Ethane exhalation in alcohol abusers was significantly, but very weakly, correlated with the daily ethanol intake before hospital admission, and the histological score for steatosis, but not with the inflammation or alcoholic hepatitis scores. Ethane exhalation was inversely correlated with the duration of abstinence before the test. In nine alcoholic patients, the exhalation of ethane was measured repeatedly, and showed slow improvement during abstinence. Ethane exhalation was significantly but weakly correlated with the Pugh's score in patients with alcoholic cirrhosis. It is concluded that the mean ethane exhalation is increased in alcohol abusers. One of the possible mechanisms may be the presence of oxidizable fat in the liver. The weak correlation with the Pugh's score is consistent with the contribution of many other factors in the progression to severe liver disease. PMID:8472992

  14. Association between alcohol consumption and symptom severity and quality of life in patients with fibromyalgia.

    PubMed

    Kim, Chul H; Vincent, Ann; Clauw, Daniel J; Luedtke, Connie A; Thompson, Jeffrey M; Schneekloth, Terry D; Oh, Terry H

    2013-03-15

    Although alcohol consumption is a common lifestyle behavior with previous studies reporting positive effects of alcohol on chronic pain and rheumatoid arthritis, no studies to this date have examined alcohol consumption in patients with fibromyalgia. We examined the association between alcohol consumption and symptom severity and quality of life (QOL) in patients with fibromyalgia. Data on self-reported alcohol consumption from 946 patients were analyzed. Subjects were grouped by level of alcohol consumption (number of drinks/week): none, low (≤ 3), moderate (>3 to 7), and heavy (>7). Five hundred and forty-six subjects (58%) did not consume alcohol. Low, moderate, and heavy levels of alcohol consumption were reported for 338 (36%), 31 (3%), and 31 patients (3%), respectively. Employment status (P <0.001), education level (P = 0.009), body mass index (P = 0.002) and opioid use (P = 0.002) differed significantly among groups with drinkers having higher education, a lower BMI, and a lower frequency of unemployment and opioid use than nondrinkers. After adjusting for these differences, the measures including the number of tender points (P = 0.01), FIQ total score (P = 0.01), physical function (P <0.001), work missed (P = 0.005), job ability (P = 0.03), and pain (P = 0.001) differed across groups, as did the SF-36 subscales of physical functioning (P <0.001), pain index (P = 0.002), general health perception (P = 0.02), social functioning (P = 0.02), and the physical component summary (P <0.001). Pairwise comparison among the 4 groups showed that the moderate and low alcohol drinkers had lower severity of fibromyalgia symptoms and better physical QOL than nondrinkers. Our study demonstrates that low and moderate alcohol consumption was associated with lower fibromyalgia symptoms and better QOL compared to no alcohol consumption. The reasons for these results are unclear. Since recent studies have demonstrated that γ-Aminobutyric Acid (GABA) levels are low in

  15. Mandatory Psychiatric Withdrawal of Severely Disturbed Students: A Study and Policy Recommendations.

    ERIC Educational Resources Information Center

    Dannells, Michael; Stuber, Donna

    1992-01-01

    Assessed frequency and nature of mandatory psychiatric withdrawal policies at Kansas colleges and universities. Forty-five of 52 colleges and universities responded to survey; of those, only 5 had specific policy for dismissing students for psychological reasons. Most respondents relied exclusively on their behavioral codes of conduct and their…

  16. An Update on CRF Mechanisms Underlying Alcohol Use Disorders and Dependence

    PubMed Central

    Quadros, Isabel Marian Hartmann; Macedo, Giovana Camila; Domingues, Liz Paola; Favoretto, Cristiane Aparecida

    2016-01-01

    Alcohol is the most commonly used and abused substance worldwide. The emergence of alcohol use disorders, and alcohol dependence in particular, is accompanied by functional changes in brain reward and stress systems, which contribute to escalated alcohol drinking and seeking. Corticotropin-releasing factor (CRF) systems have been critically implied in the transition toward problematic alcohol drinking and alcohol dependence. This review will discuss how dysregulation of CRF function contributes to the vulnerability for escalated alcohol drinking and other consequences of alcohol consumption, based on preclinical evidence. CRF signaling, mostly via CRF1 receptors, seems to be particularly important in conditions of excessive alcohol taking and seeking, including during early and protracted withdrawal, relapse, as well as during withdrawal-induced anxiety and escalated aggression promoted by alcohol. Modulation of CRF1 function seems to exert a less prominent role over low to moderate alcohol intake, or to species-typical behaviors. While CRF mechanisms in the hypothalamic–pituitary–adrenal axis have some contribution to the neurobiology of alcohol abuse and dependence, a pivotal role for extra-hypothalamic CRF pathways, particularly in the extended amygdala, is well characterized. More recent studies further suggest a direct modulation of brain reward function by CRF signaling in the ventral tegmental area, nucleus accumbens, and the prefrontal cortex, among other structures. This review will further discuss a putative role for other components of the CRF system that contribute for the overall balance of CRF function in reward and stress pathways, including CRF2 receptors, CRF-binding protein, and urocortins, a family of CRF-related peptides. PMID:27818644

  17. Insomnia severity as a mediator of the association between mental health symptoms and alcohol use in young adult veterans.

    PubMed

    Miller, Mary Beth; DiBello, Angelo M; Carey, Kate B; Borsari, Brian; Pedersen, Eric R

    2017-08-01

    Prior research has documented associations between mental health and alcohol use, mental health and insomnia, and insomnia and alcohol use. This study examined insomnia severity as a mediator of the association between mental health and alcohol-related outcomes in young adult veterans. Veterans aged 18-34 years (N=622, 83% male) who reported drinking in the past year completed assessments at baseline and one-month follow-up as part of a larger intervention trial. Participants reported symptoms of depression and posttraumatic stress disorder (PTSD) at baseline, insomnia severity at one month, and alcohol use and related consequences at baseline and one month. Mediation analyses using bootstrapped confidence intervals were used to examine the indirect effects of baseline mental health symptoms on alcohol-related outcomes at one month via insomnia severity. Insomnia severity was associated with both drinking quantity and alcohol-related consequences. Greater depressive (but not PTSD) symptoms were associated directly with more alcohol-related consequences. Neither depressive nor PTSD symptoms had direct effects on drinking quantity when controlling for the other mental health symptoms (e.g., depressive symptoms did not predict drinking quantity when controlling for symptoms of PTSD). However, symptoms of depression and PTSD predicted drinks per week and alcohol-related consequences indirectly through insomnia severity. Symptoms of depression and PTSD increase risk for alcohol use and related consequences in part by increasing symptoms of insomnia. Findings suggest that insomnia may be an appropriate target for prevention and intervention efforts among heavy-drinking Veterans reporting symptoms of depression or PTSD. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Kratom (Mitragyna speciosa) dependence, withdrawal symptoms and craving in regular users.

    PubMed

    Singh, Darshan; Müller, Christian P; Vicknasingam, Balasingam K

    2014-06-01

    Kratom (Mitragyna speciosa) preparations have been traditionally used in Southeast Asia for its medicinal properties. Lately, Kratom use has spread to Europe and the US, where abuse potential and health hazards increasingly emerge. This study is the first to measure systematically Kratom dependence, withdrawal symptoms, and drug craving in regular Kratom users in Malaysia. A cross-sectional survey of 293 regular Kratom users was conducted in the community across three northern peninsular states of Malaysia. The Leeds Dependence Questionnaire, Marijuana Withdrawal Checklist, and Marijuana Craving Questionnaire-Short Form were used to measure Kratom dependence, withdrawal and craving. More than half of the regular users (>6 month of use) developed severe Kratom dependence problems, while 45% showed a moderate Kratom dependence. Physical withdrawal symptoms commonly experienced include muscle spasms and pain, sleeping difficulty, watery eyes/nose, hot flashes, fever, decreased appetite, and diarrhoea. Psychological withdrawal symptoms commonly reported were restlessness, tension, anger, sadness, and nervousness. The average amount of the psychoactive compound, mitragynine, in a single dose of a Kratom drink was 79mg, suggesting an average daily intake of 276.5mg. Regular users who consumed ≥3 glasses Kratom per day, had higher odds of developing severe Kratom dependence, withdrawal symptoms, and inability to control Kratom craving. The findings from this study show that regular Kratom use is associated with drug dependency, development of withdrawal symptoms, and craving. These symptoms become more severe with prolonged use and suggest a stronger control of the drug. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Marijuana withdrawal and aggression among a representative sample of U.S. marijuana users

    PubMed Central

    Smith, Philip H.; Homish, Gregory G.; Leonard, Kenneth E.; Collins, R. Lorraine

    2013-01-01

    Background Previous laboratory-based research suggests that withdrawal from marijuana may cause increased aggression. It is unclear whether this finding extends beyond the laboratory setting to the general population of marijuana users. The purpose of this study was to test a cross-sectional association between marijuana withdrawal symptoms and aggression among a representative sample of U.S. adult marijuana users, and to test whether this association was moderated by previous history of aggression. Methods Data were analyzed from the National Epidemiologic Survey on Alcohol and Related Conditions. Wave Two data (2004–2005) were used for all variables except for history of aggression, which was assessed during the Wave One interview (2001–2002). Two outcomes were examined: self-report general aggression and relationship aggression. Odds ratios for aggression based on withdrawal symptoms and the interaction between withdrawal symptoms and history of aggression were calculated using logistic regression, adjusting for covariates and accounting for the complex survey design. Results Among marijuana users with a history of aggression, marijuana withdrawal was associated with approximately 60% higher odds of past year relationship aggression (p < 0.05). There was no association between withdrawal symptoms and relationship aggression among those without a history of aggression, and no association with general aggression regardless of history of aggression. Conclusions The findings from this study support the notion that laboratory-based increases in aggression due to marijuana withdrawal extend to the general population of marijuana users who have a previous history of aggression. PMID:23380439

  20. Suicidal Behavior and Alcohol Abuse

    PubMed Central

    Pompili, Maurizio; Serafini, Gianluca; Innamorati, Marco; Dominici, Giovanni; Ferracuti, Stefano; Kotzalidis, Giorgio D.; Serra, Giulia; Girardi, Paolo; Janiri, Luigi; Tatarelli, Roberto; Sher, Leo; Lester, David

    2010-01-01

    Suicide is an escalating public health problem, and alcohol use has consistently been implicated in the precipitation of suicidal behavior. Alcohol abuse may lead to suicidality through disinhibition, impulsiveness and impaired judgment, but it may also be used as a means to ease the distress associated with committing an act of suicide. We reviewed evidence of the relationship between alcohol use and suicide through a search of MedLine and PsychInfo electronic databases. Multiple genetically-related intermediate phenotypes might influence the relationship between alcohol and suicide. Psychiatric disorders, including psychosis, mood disorders and anxiety disorders, as well as susceptibility to stress, might increase the risk of suicidal behavior, but may also have reciprocal influences with alcohol drinking patterns. Increased suicide risk may be heralded by social withdrawal, breakdown of social bonds, and social marginalization, which are common outcomes of untreated alcohol abuse and dependence. People with alcohol dependence or depression should be screened for other psychiatric symptoms and for suicidality. Programs for suicide prevention must take into account drinking habits and should reinforce healthy behavioral patterns. PMID:20617037

  1. Targeting Dynorphin/Kappa Opioid Receptor Systems to Treat Alcohol Abuse and Dependence

    PubMed Central

    Walker, Brendan M.; Valdez, Glenn R.; McLaughlin, Jay P.; Bakalkin, Georgy

    2012-01-01

    This review represents the focus of a symposium that was presented at the “Alcoholism and Stress: A Framework for Future Treatment Strategies” conference in Volterra, Italy on May 3–6, 2011 and organized / chaired by Dr. Brendan M. Walker. The primary goal of the symposium was to evaluate and disseminate contemporary findings regarding the emerging role of kappa-opioid receptors (KORs) and their endogenous ligands dynorphins (DYNs) in the regulation of escalated alcohol consumption, negative affect and cognitive dysfunction associated with alcohol dependence, as well as DYN / KOR mediation of the effects of chronic stress on alcohol reward and seeking behaviors. Dr. Glenn Valdez described a role for KORs in the anxiogenic effects of alcohol withdrawal. Dr. Jay McLaughlin focused on the role of KORs in repeated stress-induced potentiation of alcohol reward and increased alcohol consumption. Dr. Brendan Walker presented data characterizing the effects of KOR antagonism within the extended amygdala on withdrawal-induced escalation of alcohol self-administration in dependent animals. Dr. Georgy Bakalkin concluded with data indicative of altered DYNs and KORs in the prefrontal cortex of alcohol dependent humans that could underlie diminished cognitive performance. Collectively, the data presented within this symposium identified the multifaceted contribution of KORs to the characteristics of acute and chronic alcohol-induced behavioral dysregulation and provided a foundation for the development of pharmacotherapeutic strategies to treat certain aspects of alcohol use disorders. PMID:22459870

  2. Prolonged social withdrawal disorder: a hikikomori case in Spain.

    PubMed

    Ovejero, Santiago; Caro-Cañizares, Irene; de León-Martínez, Victoria; Baca-Garcia, Enrique

    2014-09-01

    The Japanese term hikikomori means literally 'to be confined'. Social withdrawal can be present in severe psychiatric disorders; however, in Japan, hikikomori is a defined nosologic entity. There have been only a few reported cases in occidental culture. We present a case report of a Spanish man with prolonged social withdrawal lasting for 4 years. This is a case of prolonged social withdrawal not bound to culture, as well as the second case of hikikomori reported in Spain. We propose prolonged social withdrawal disorder as a disorder not linked to culture, in contrast to hikikomori. Further documentation of this disorder is still needed to encompass all cases reported in Japan and around the world. © The Author(s) 2013.

  3. Cannabis Withdrawal, Posttreatment Abstinence, and Days to First Cannabis Use Among Emerging Adults in Substance Use Treatment: A Prospective Study

    PubMed Central

    Davis, Jordan P.; Smith, Douglas C.; Morphew, Jason W.; Lei, Xinrong; Zhang, Saijun

    2015-01-01

    Very little prospective research investigates how cannabis withdrawal is associated with treatment outcomes, and this work has not used the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) thresholds for cannabis withdrawal. The sample included 110 emerging adults entering outpatient substance use treatment who were heavy cannabis users with no other drug use and limited alcohol use. We used survival analyses to predict days to first use of cannabis and logistic regression to predict whether participants were abstinent and living in the community at 3 months. Those meeting criteria for cannabis withdrawal were more likely to return to use sooner than those not meeting criteria for cannabis withdrawal. However, the presence of cannabis withdrawal was not a significant predictor of 3-month abstinence. Emerging adults with DSM-5 cannabis withdrawal may have difficulty initiating abstinence in the days following their intake assessment, implying the need for strategies to mitigate their more rapid return to cannabis use. PMID:26877548

  4. Predictive factors for the severity of liver fibrosis in patients with chronic hepatitis C and moderate alcohol consumption.

    PubMed

    Vădan, Roxana; Gheorghe, Liana; Becheanu, Gabriel; Iacob, Răzvan; Iacob, Speranţa; Gheorghe, Cristian

    2003-09-01

    Among the histological lesions seen in chronic hepatitis C (CHC), the presence of steatosis, bile duct lesions and lymphoid aggregates are characteristic. Recent reports suggest that steatosis is an independent risk factor for liver fibrosis in CHC. The aim of our study was to determine the relative contribution of steatosis and moderate alcohol consumption to the severity of liver fibrosis in patients infected with genotype 1 hepatitis C virus. We evaluated the patients with biopsy proven CHC and no or only moderate alcohol intake (<40 g/day). The demographical parameters of the study population, the indices of alcohol consumption: erythrocyte median corpuscular volume (MCV), gamma-glutamyl transpeptidase (GGT), the histological characteristics were noted and a statistical analysis was performed in order to determine the factors independently associated with severe fibrosis and with severe steatosis. From the 200 patients included in the study, 82 were males and 118 females, with a mean age of 47.75+/-10.42 years. At univariate analysis, advanced (grade 2, 3) fibrosis correlated with: the age at the time of biopsy, increased inflammatory activity (HAI), moderate/severe steatosis, alcohol intake, elevated GGT and MCV values. After multivariate logistic regression only age, HAI and steatosis were independently associated with advanced fibrosis stage. Regarding hepatic steatosis, from the factors found to correlate with severe steatosis at univariate analysis (alcohol intake, elevated GGT and MCV levels, severe fibrosis), after multivariate logistic regression only the elevated level of GGT was an independent prognostic factor for severe steatosis. Steatosis is an important risk factor for the severity of liver disease in CHC patients. Among patients with genotype 1 hepatitis C virus infection and moderate alcohol intake, those with serum levels of GGT over two times the normal value are at high risk for severe steatosis.

  5. Observing nurses has improved my alcohol dependency care.

    PubMed

    Jaques, Ellise

    2016-09-21

    My first placement in my first year of nursing training was on a gastrointestinal/hepatology ward. Alongside my mentor, I was caring for a patient who had been withdrawing from alcohol since admission to hospital the previous evening.

  6. Relationship Between Emotional Processing, Drinking Severity and Relapse in Adults Treated for Alcohol Dependence in Poland

    PubMed Central

    Kopera, Maciej; Jakubczyk, Andrzej; Suszek, Hubert; Glass, Jennifer M.; Klimkiewicz, Anna; Wnorowska, Anna; Brower, Kirk J.; Wojnar, Marcin

    2015-01-01

    Aims: Growing data reveals deficits in perception, understanding and regulation of emotions in alcohol dependence (AD). The study objective was to explore the relationships between emotional processing, drinking history and relapse in a clinical sample of alcohol-dependent patients. Methods: A group of 80 inpatients entering an alcohol treatment program in Warsaw, Poland was recruited and assessed at baseline and follow-up after 12 months. Baseline information about demographics, psychopathological symptoms, personality and severity of alcohol problems was obtained. The Schutte Self-Report Emotional Intelligence (EI) Test and Toronto Alexithymia Scale (TAS) were utilized for emotional processing assessment. Follow-up information contained data on drinking alcohol during the last month. Results: At baseline assessment, the duration of alcohol drinking was associated with lower ability to utilize emotions. Patients reporting more difficulties with describing feelings drank more during their last episode of heavy drinking, and had a longer duration of intensive alcohol use. A longer duration of the last episode of heavy drinking was associated with more problems identifying and regulating emotions. Poor utilization of emotions and high severity of depressive symptoms contributed to higher rates of drinking at follow-up. Conclusions: These results underline the importance of systematic identification of discrete emotional problems and dynamics related to AD. This knowledge has implications for treatment. Psychotherapeutic interventions to improve emotional skills could be utilized in treatment of alcohol-dependent patients. PMID:25543129

  7. Motivation to change as a mediator for the longitudinal relationships of gender and alcohol severity with one-year drinking outcome.

    PubMed

    Small, Jeon; Ounpraseuth, Songthip; Curran, Geoffrey M; Booth, Brenda M

    2012-05-01

    We examined whether motivation to change mediated the relationships between gender and baseline alcohol severity with drinking outcome at 12-month follow-up in a longitudinal community sample. Data were from baseline and 12-month interviews from the Rural Alcohol Study, a probability sample of rural and urban at-risk drinkers (N = 733) from six southern states. At-risk drinkers were identified through a telephone-screening interview. Measures of motivation (problem recognition and taking action) were the resultant two factors derived from the Stages of Change Readiness and Treatment Eagerness Scale. Items on social consequences of drinking measured alcohol severity. Structural equation models examined relationships between baseline alcohol severity and motivation with drinks per drinking day at 12 months. We identified significant, direct paths between drinking at 12 months and alcohol severity and taking action with an unstandardized estimate of 0.116 (p < .05), alcohol severity and problem recognition (0.423, p < .01), and each of the two "motivation" latent constructs-problem recognition (1.846, p < .01) and taking action (-0.660, p < .01). Finally, the combined direct and negative effect of gender on alcohol consumption at 12-month follow-up was statistically significant, with an unstandardized estimate of -0.970 (p < .01). The current study offers evidence for motivation to change as a viable mechanism through which alcohol severity is associated with subsequent drinking outcomes. More research is needed to further explore the persistence of motivation to change on drinking outcomes over time.

  8. Severity of acute illness is associated with baseline readiness to change in medical intensive care unit patients with unhealthy alcohol use.

    PubMed

    Clark, Brendan J; Smart, Alexandra; House, Robert; Douglas, Ivor; Burnham, Ellen L; Moss, Marc

    2012-03-01

    Unhealthy alcohol use predisposes to multiple conditions that frequently result in critical illness and is present in up to one-third of patients admitted to a medical intensive care unit (ICU). We sought to determine the baseline readiness to change in medical ICU patients with unhealthy alcohol use and hypothesized that the severity of acute illness would be independently associated with higher scores on readiness to change scales. We further sought to determine whether this effect is modified by the severity of unhealthy alcohol use. We performed a cross-sectional observational study of current regular drinkers in 3 medical ICUs. The Alcohol Use Disorders Identification Test was used to differentiate low-risk and unhealthy alcohol use and further categorize patients into risky alcohol use or an alcohol use disorder. The severity of a patient's acute illness was assessed by calculating the Acute Physiologic and Chronic Health Evaluation II (APACHE II) score at the time of admission to the medical ICU. Readiness to change was assessed using standardized questionnaires. Of 101 medical ICU patients who were enrolled, 65 met the criteria for unhealthy alcohol use. The association between the severity of acute illness and readiness to change depended on the instrument used. A higher severity of illness measured by APACHE II score was an independent predictor of readiness to change as assessed by the Stages of Change Readiness and Treatment Eagerness Scale (Taking Action scale; p < 0.01). When a visual analog scale was used to assess readiness to change, there was a significant association with severity of acute illness (p < 0.01) that was modified by the severity of unhealthy alcohol use (p = 0.04 for interaction term). Medical ICU patients represent a population where brief interventions require further study. Studies of brief intervention should account for the severity of acute illness and the severity of unhealthy alcohol use as potential effect modifiers

  9. Family Stress and Coping From Hospitalization of Clients With Severe Alcohol Use Disorder in Korea.

    PubMed

    Park, Gyu-Hee; Choi, Yun-Jung

    The rate of relapse and involuntary hospitalization among clients with alcohol use disorder exceeds 40% in South Korea. As a result, family members of clients experience considerable stress and require the assistance of professional services. This empirical study investigates levels of perceived stress and stress coping styles among family members of clients with severe alcohol use disorder and examines the correlations among these variables. Data were collected from three inpatient alcohol rehabilitation centers and five psychiatric hospitals in South Korea. Family stress levels and stress coping styles for 133 respondents were evaluated using the Hospital Stress Rating Scale for Family Members and the Stress Coping Style Checklist. There were significant differences in stress levels according to whether participants had attended a family educational program in the past or were doing so presently. Furthermore, significant differences in stress were observed among participants who were using the stress coping style of easing strained emotions during the client's hospitalization but who had never attended an educational program. Among the subcategories, stress levels had especially strong relationships with easing strained emotions, seeking advice, and solving problems. The results showed that families with severe alcohol use disorder experience stress from the client's hospitalization and seek advice from neighbors to deal with worries, privacy concerns, and economic problems. Family interventions are needed to provide family members with strategies to cope with stress, which can support recovery of clients with severe alcohol use disorder.

  10. Memantine reduces alcohol drinking but not relapse in alcohol-dependent rats.

    PubMed

    Alaux-Cantin, Stéphanie; Buttolo, Romain; Houchi, Hakim; Jeanblanc, Jérôme; Naassila, Mickaël

    2015-09-01

    Alcoholism is a chronic relapsing disorder with consequences on health and that requires more effective treatments. Among alternative therapies, the therapeutic potential of the non-competitive N-methyl-D-aspartate receptor antagonist memantine has been suggested. Despite promising results, its efficiency in the treatment of alcoholism remains controversial. Currently, there is no pre-clinical data regarding its effects on the motivation for ethanol in post-dependent (PD) animals exposed to intermittent ethanol vapor, a validated model of alcoholism. Thus, the objectives of this study were to evaluate the effects of acute injections of memantine (0, 12.5, 25 and 50 mg/kg) on operant ethanol self-administration in non-dependent (ND) and PD rats tested either during acute withdrawal or relapse after protracted abstinence. Our results showed that memantine (25 mg/kg) abolished ethanol self-administration in ND rats and reduced by half the one of PD rats during acute withdrawal. While this effect was observed only 6 hours after treatment in ND rats, it was long lasting in PD rats (at least 30 hours after injection). Furthermore, our results indicated that memantine did not modify the breaking point for ethanol. This suggests that memantine probably act by potentiating the pharmacological effect of ethanol but not by reducing motivation for ethanol. Finally, memantine was also ineffective in reducing relapse after protracted abstinence. Altogether, our pre-clinical results highlighted a potential therapeutic use of memantine that may be used as a replacement therapy drug but not as relapse-preventing drug. © 2014 Society for the Study of Addiction.

  11. Psychometric properties of the Spanish version of the Cocaine Selective Severity Assessment to evaluate cocaine withdrawal in treatment-seeking individuals.

    PubMed

    Pérez de los Cobos, José; Trujols, Joan; Siñol, Núria; Vasconcelos e Rego, Lisiane; Iraurgi, Ioseba; Batlle, Francesca

    2014-09-01

    Reliable and valid assessment of cocaine withdrawal is relevant for treating cocaine-dependent patients. This study examined the psychometric properties of the Spanish version of the Cocaine Selective Severity Assessment (CSSA), an instrument that measures cocaine withdrawal. Participants were 170 cocaine-dependent inpatients receiving detoxification treatment. Principal component analysis revealed a 4-factor structure for CSSA that included the following components: 'Cocaine Craving and Psychological Distress', 'Lethargy', 'Carbohydrate Craving and Irritability', and 'Somatic Depressive Symptoms'. These 4 components accounted for 56.0% of total variance. Internal reliability for these components ranged from unacceptable to good (Chronbach's alpha: 0.87, 0.65, 0.55, and 0.22, respectively). All components except Somatic Depressive Symptoms presented concurrent validity with cocaine use. In summary, while some properties of the Spanish version of the CSSA are satisfactory, such as interpretability of factor structure and test-retest reliability, other properties, such as internal reliability and concurrent validity of some factors, are inadequate. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Mitragynine Attenuates Withdrawal Syndrome in Morphine-Withdrawn Zebrafish

    PubMed Central

    Khor, Beng-Siang; Amar Jamil, Mohd Fadzly; Adenan, Mohamad Ilham; Chong Shu-Chien, Alexander

    2011-01-01

    A major obstacle in treating drug addiction is the severity of opiate withdrawal syndrome, which can lead to unwanted relapse. Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawal phase. Adult zebrafish were subjected to two weeks chronic morphine exposure at 1.5 mg/L, followed by withdrawal for 24 hours prior to tests. Using the novel tank diving tests, we first showed that morphine-withdrawn zebrafish display anxiety-related swimming behaviors such as decreased exploratory behavior and increased erratic movement. Morphine withdrawal also elevated whole-body cortisol levels, which confirms the phenotypic stress-like behaviors. Exposing morphine-withdrawn fish to mitragynine however attenuates majority of the stress-related swimming behaviors and concomitantly lower whole-body cortisol level. Using real-time PCR gene expression analysis, we also showed that mitragynine reduces the mRNA expression of corticotropin releasing factor receptors and prodynorphin in zebrafish brain during morphine withdrawal phase, revealing for the first time a possible link between mitragynine's ability to attenuate anxiety during opiate withdrawal with the stress-related corticotropin pathway. PMID:22205946

  13. Cannabis Withdrawal Among Detained Adolescents: Exploring the Impact of Nicotine and Race.

    PubMed

    Soenksen, Shayna; Stein, L A R; Brown, Joanna D; Stengel, JoAnn R; Rossi, Joseph S; Lebeau, Rebecca

    2015-04-01

    Rates of marijuana use among detained youths are exceptionally high. Research suggests a cannabis withdrawal syndrome is valid and clinically significant; however, these studies have mostly been conducted in highly controlled laboratory settings with treatment-seeking, White adults. The present study analyzed archival data to explore the magnitude of cannabis withdrawal symptoms within a diverse sample of detained adolescents while controlling for tobacco use and investigating the impact of race on symptom reports. Adolescents recruited from a juvenile correctional facility (N=93) completed a background questionnaire and the Marijuana Withdrawal Checklist. Analyses revealed a significant main effect for level of tobacco use on severity of irritability, and for level of marijuana use on severity of craving to smoke marijuana and strange/wild dreams. Furthermore, a significant main effect for race was found with Black adolescents reporting lower withdrawal discomfort scores and experiencing less severe depressed mood, difficulty sleeping, nervousness/anxiety, and strange/wild dreams. Although exploratory, these findings may have significant clinical implications for providers in juvenile detention facilities, allowing the execution of proper medical and/or behavioral interventions to assist adolescents presenting with problematic cannabis and/or tobacco withdrawal.

  14. Voluntary Co-Consumption of Alcohol and Nicotine: Effects of Abstinence, Intermittency, and Withdrawal in Mice

    PubMed Central

    O’Rourke, Kyu Y.; Touchette, Jillienne C.; Hartell, Elizabeth C.; Bade, Elizabeth J.; Lee, Anna M.

    2018-01-01

    Alcohol and nicotine are often used together, and there is a high rate of co-occurrence between alcohol and nicotine addiction. Most animal models studying alcohol and nicotine interactions have utilized passive drug administration, which may not be relevant to human co-addiction. In addition, the interactions between alcohol and nicotine in female animals have been understudied, as most studies have used male animals. To address these issues, we developed models of alcohol and nicotine co-consumption in male and female mice that utilized voluntary, oral consumption of unsweetened alcohol, nicotine and water. We first examined drug consumption and preference in single-drug, sequential alcohol and nicotine consumption tests in male and female C57BL/6 and DBA/2J mice. We then tested chronic continuous and intermittent access alcohol and nicotine co-consumption procedures. We found that male and female C57BL/6 mice readily co-consumed unsweetened alcohol and nicotine. In our continuous co-consumption procedures, we found that varying the available nicotine concentration during an alcohol abstinence period affected compensatory nicotine consumption during alcohol abstinence, and affected rebound alcohol consumption when alcohol was re-introduced. Consumption of alcohol and nicotine in an intermittent co-consumption procedure produced higher alcohol consumption levels, but not nicotine consumption levels, compared with the continuous co-consumption procedures. Finally, we found that intermittent alcohol and nicotine co-consumption resulted in physical dependence. Our data show that these voluntary co-consumption procedures can be easily performed in mice and can be used to study behavioral interactions between alcohol and nicotine consumption, which may better model human alcohol and nicotine co-addiction. PMID:27342124

  15. Low effective organizational strategies in visual memory performance of unmedicated alcoholics during early abstinence.

    PubMed

    Daig, Isolde; Mahlberg, Richard; Schroeder, Franziska; Gudlowski, Yehonala; Wrase, Jana; Wertenauer, Florian; Bschor, Tom; Esser, Guenter; Heinz, Andreas; Kienast, Thorsten

    2010-12-14

    Alcohol-dependent patients in early abstinence show an impairment of cognitive functions which can be seen in poor implementation of newly learned skills for avoiding relapse. Executive dysfunction may persist during abstinence in alcohol-dependent persons, thus mitigating long-term abstinence. This study assessed visual memory function and choice of organizational strategies in alcoholics, as these are major factors necessary to implement ongoing behavior changes which are required for maintaining abstinence. We investigated 25 severely alcohol-dependent male patients between days 7 to 10 of abstinence, immediately after clinical withdrawal symptoms have ceased, compared to 15 healthy age, sex, and education matched controls. Pharmacological therapy had been terminated at least four half-lifes before inclusion into the study. Visual perceptual learning and organizational strategies were assessed with the Rey-Osterrieth Complex Figure Test (R-OCF). There were no group differences in copying or recalling the figure, but time differences occurred. Alcoholics and healthy controls performed worse in recalling than in copying. But, alcoholics used less effective organizational strategies. There was a deficit in choice of organizational strategy in newly abstinent and unmedicated alcohol-dependent patients. Due to the imperfect organizational strategies, alcoholics might need auxiliary therapeutic care to strengthen their cognitive ability.

  16. Trends in alcohol use during moderate and severe traumatic brain injury: 18 years of neurotrauma in Pennsylvania.

    PubMed

    Bernier, R A; Hillary, F G

    2016-01-01

    Alcohol is a known risk factor for TBI, yet little is known about how rates of alcohol use at time of injury differ across demographics and the stability of alcohol-related injury over time. Further, findings examining the relationship between alcohol and outcome are mixed. This study aimed to examine changes in alcohol-positive moderate-to-severe traumatic brain injury (+aTBI) over two decades with focus on demographic factors, changes in +aTBI frequency over time, mortality and acute outcome. This retrospective study examined data collected from 1992-2009 by the Pennsylvania Trauma Outcome Study (PTOS). Results reveal that the proportion of +aTBI has been generally stable across years. However, there is an interaction of +aTBI incidence with mechanism of injury and age, with a downward trend in +aTBI within MVA and fall and individuals 18-30 and 71+ years. Further, consistent with several findings in the literature, alcohol was associated with higher rates of survival and better FSD scores during acute recovery. This study discusses findings in the context of a greater literature on TBI-related alcohol and outcome. The injury-alcohol profiles highlighted could be used to inform future allocation of resources toward prevention of, intervention for and care of individuals who sustain TBI.

  17. Alcohol use disorders in pregnancy.

    PubMed

    DeVido, Jeffrey; Bogunovic, Olivera; Weiss, Roger D

    2015-01-01

    Alcohol use disorders (AUDs) are less prevalent in pregnant women than in nonpregnant women, but these disorders can create a host of clinical challenges when encountered. Unfortunately, little evidence is available to guide clinical decision making in this population. Drinking alcohol during pregnancy can have negative consequences on both fetus and mother, but it remains controversial as to the volume of alcohol consumption that correlates with these consequences. Likewise, little evidence is available to support the use of particular pharmacologic interventions for AUDs during pregnancy or to guide the management of alcohol detoxification in pregnant women. The use of benzodiazepines (the mainstay of most alcohol detoxification protocols) in pregnant women is controversial. Nevertheless, despite the lack of robust data to guide management of AUDs in pregnancy, clinicians need to make management decisions when confronted with these challenging situations. In that context, this article reviews the epidemiology of AUDs in pregnancy and the pharmacologic management of both AUDs and alcohol withdrawal in pregnant women, with the goal of informing clinicians about what is known about managing these co-occurring conditions.

  18. Alcohol Use Disorders in Pregnancy

    PubMed Central

    DeVido, Jeffrey; Bogunovic, Olivera; Weiss, Roger D.

    2015-01-01

    Alcohol use disorders (AUD) during pregnancy are less prevalent than in non-pregnant women, but they can create a host of clinical challenges when encountered. Unfortunately, there is little research information available to guide clinical decision-making in this population. Drinking alcohol during pregnancy can have negative consequences on both fetus and mother, but there is controversy regarding the volume of alcohol consumption that correlates with these consequences. There is little evidence to support the use of pharmacologic interventions for AUD during pregnancy. Similarly, there are few data to guide management of alcohol detoxification in pregnant women, and the use of benzodiazepines (the mainstay of most alcohol detoxification protocols) in pregnant women is controversial. Despite a lack of robust data to guide management of AUDs in pregnancy, clinicians must nonetheless make management decisions when confronted with these challenging situations. Therefore, this paper reviews the epidemiology of AUDs in pregnancy, and the pharmacologic management of both AUDs and alcohol withdrawal in pregnant women, to better inform clinicians about what is known about managing these co-occurring conditions. PMID:25747924

  19. Severity of Acute Illness is Associated with Baseline Readiness to Change in Medical Intensive Care Unit Patients with Unhealthy Alcohol Use

    PubMed Central

    Clark, Brendan J.; Smart, Alexandra; House, Robert; Douglas, Ivor; Burnham, Ellen L.; Moss, Marc

    2011-01-01

    Introduction Unhealthy alcohol use predisposes to multiple conditions that frequently result in critical illness and is present in up to one-third of patients admitted to a medical intensive care unit (ICU). We sought to determine the baseline readiness to change in medical ICU patients with unhealthy alcohol use and hypothesized that the severity of acute illness would be independently associated with higher scores on readiness to change scales. We further sought to determine whether this effect is modified by the severity of unhealthy alcohol use. Materials and Methods We performed a cross-sectional observational study of current regular drinkers in three medical ICUs. The Alcohol Use Disorders Identification Test was used to differentiate low risk and unhealthy alcohol use and further categorize patients into risky alcohol use or an alcohol use disorder. The severity of a patient’s acute illness was assessed by calculating the Acute Physiology and Chronic Healthy Evaluation II score at the time of admission to the medical ICU. Readiness to change was assessed using standardized questionnaires. Results Of 101 medical ICU patients who were enrolled, 65 met the criteria for unhealthy alcohol use. The association between the severity of acute illness and readiness to change depended on the instrument used. A higher severity of illness measured by APACHEII score was an independent predictor of readiness to change as assessed by the Stages of Change Readiness and Treatment Eagerness Scale (Taking Action scale) (p< 0.01). When a visual analog scale was used to assess readiness to change, there was a significant association with severity of acute illness (p < 0.01) that was modified by the severity of unhealthy alcohol use (p = 0.04 for interaction term). Conclusion Medical ICU patients represent a population where brief interventions require further study. Studies of brief intervention should account for the severity of acute illness and the severity of unhealthy

  20. ALCOHOL USE BY URBAN BICYCLISTS IS ASSOCIATED WITH MORE SEVERE INJURY, GREATER HOSPITAL RESOURCE USE, AND HIGHER MORTALITY

    PubMed Central

    Sethi, Monica; Heyer, Jessica; Wall, Stephen; DiMaggio, Charles; Shinseki, Matthew; Slaughter, Dekeya; Frangos, Spiros G

    2017-01-01

    Alcohol use is a risk factor for severe injury in pedestrians struck by motor vehicles. Our objective was to investigate alcohol use by bicyclists and its effects on riding behaviors, medical management, injury severity, and mortality within a congested urban setting. A hospital-based, observational study of injured bicyclists presenting to a Level I regional trauma center in New York City was conducted. Data were collected prospectively from 2012 to 2014 by interviewing all bicyclists presenting within 24 h of injury and supplemented with medical record review. Variables included demographic characteristics, scene-related data, Glasgow Coma Scale (GCS), computed tomography (CT) scans, and clinical outcomes. Alcohol use at the time of injury was determined by history or blood alcohol level (BAL) >0.01 g/dL. Of 689 bicyclists, 585 (84.9%) were male with a mean age of 35.2. One hundred four (15.1%) bicyclists had consumed alcohol prior to injury. Alcohol use was inversely associated with helmet use (16.5% [9.9–25.1] vs. 43.2% [39.1–47.3]). Alcohol-consuming bicyclists were more likely to fall from their bicycles (42.0% [32.2–52.3] vs. 24.2% [20.8–27.9]) and less likely to be injured by collision with a motor vehicle (52.0% [41.7–62.1] vs. 67.5% [63.5–71.3]). 80% of alcohol-consuming bicyclists underwent CT imaging at presentation compared with 51.5% of non-users. Mortality was higher among injured bicyclists who had used alcohol (2.9% [0.6–8.2] vs. 0.0% [0.0–0.6]). Adjusted multivariable analysis revealed that alcohol use was independently associated with more severe injury (Adjusted Odds Ratio 2.27, p = 0.001, 95% Confidence Interval 1.40–3.68). Within a dense urban environment, alcohol use by bicyclists was associated with more severe injury, greater hospital resource use, and higher mortality. As bicycling continues to increase in popularity internationally, it is important to heighten awareness about the risks and consequences of bicycling while

  1. Severity of alcohol use and problem behaviors among school-based youths in Puerto Rico

    PubMed Central

    Latimer, William W.; Rojas, Vanessa Cecilia; Mancha, Brent Edward

    2009-01-01

    Objectives The present study sought to: (a) categorize youths into groups based on their level of alcohol use and number of symptoms of alcohol abuse and dependence defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), and (b) examine whether these categories were associated with other problem behaviors in which youths engage (marijuana use, sexual intercourse, and having been arrested or having trouble with the law). Methods The study is based on a cross-sectional survey administered to 972 school-based youths from one middle school and one high school in San Juan, Puerto Rico. Youths were categorized based on their alcohol use and alcohol problems. These categories were then examined for associations with lifetime marijuana use, lifetime sexual intercourse, and having been arrested or having had trouble with the law in the past year. The original eight categories of alcohol use were collapsed into six categories based on the results. Results For virtually every group characterized by higher severity of alcohol use and alcohol problems, researchers found an increasing prevalence of marijuana use in their lifetimes, increasing odds of sexual intercourse in their lifetimes, and having had trouble with the law in the past year. Conclusions Knowing about variations in alcohol use and alcohol problems may be instrumental in measuring the degree to which youths may also be engaging in a range of other elevated risk behaviors and a progression to more serious forms of alcohol and drug use. PMID:18510792

  2. Orbitofrontal structural markers of negative affect in alcohol dependence and their associations with heavy relapse-risk at 6 months post-treatment.

    PubMed

    Zois, E; Vollstädt-Klein, S; Hoffmann, S; Reinhard, I; Charlet, K; Beck, A; Jorde, A; Kirsch, M; Walter, H; Heinz, A; Kiefer, F

    2017-10-01

    Alcohol relapse is often occurring to regulate negative affect during withdrawal. On the neurobiological level, alcoholism is associated with gray matter (GM) abnormalities in regions that regulate emotional experience such as the orbitofrontal cortex (OFC). However, no study to our knowledge has investigated the neurobiological unpinning of affect in alcoholism at early withdrawal and the associations of OFC volume with long-term relapse risk. One hundred and eighty-two participants were included, 95 recently detoxified alcohol dependent patients (ADP) and 87 healthy controls (HC). We measured affective states using the positive and negative affect schedule (PANAS). We collected T1-weighted brain structural images and performed Voxel-based morphometry (VBM). Findings revealed GM volume decrease in alcoholics in the prefrontal cortex (including medial OFC), anterior cingulate gyrus, and insula. GM volume in the medial OFC was positively associated with NA in the ADP group. Cox regression analysis predicted that risk to heavy relapse at 6 months increases with decreased GM volume in the medial OFC. Negative affect during alcohol withdrawal was positively associated with OFC volume. What is more, increased GM volume in the OFC also moderated risk to heavy relapse at 6 months. Reduced GM in the OFC poses as risk to recovery from alcohol dependence and provides valuable insights into transient negative affect states during withdrawal that can trigger relapse. Implications exist for therapeutic interventions signifying the OFC as a neurobiological marker to relapse and could explain the inability of ADP to regulate internal negative affective states. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Association between alcohol consumption and symptom severity and quality of life in patients with fibromyalgia

    PubMed Central

    2013-01-01

    Introduction Although alcohol consumption is a common lifestyle behavior with previous studies reporting positive effects of alcohol on chronic pain and rheumatoid arthritis, no studies to this date have examined alcohol consumption in patients with fibromyalgia. We examined the association between alcohol consumption and symptom severity and quality of life (QOL) in patients with fibromyalgia. Methods Data on self-reported alcohol consumption from 946 patients were analyzed. Subjects were grouped by level of alcohol consumption (number of drinks/week): none, low (≤3), moderate (>3 to 7), and heavy (>7). Univariate analyses were used to find potential confounders, and analysis of covariance was used to adjust for these confounders. Tukey HSD pairwise comparisons were used to determine differences between alcohol groups. Results Five hundred and forty-six subjects (58%) did not consume alcohol. Low, moderate, and heavy levels of alcohol consumption were reported for 338 (36%), 31 (3%), and 31 patients (3%), respectively. Employment status (P <0.001), education level (P = 0.009), body mass index (P = 0.002) and opioid use (P = 0.002) differed significantly among groups with drinkers having higher education, a lower BMI, and a lower frequency of unemployment and opioid use than nondrinkers. After adjusting for these differences, the measures including the number of tender points (P = 0.01), FIQ total score (P = 0.01), physical function (P <0.001), work missed (P = 0.005), job ability (P = 0.03), and pain (P = 0.001) differed across groups, as did the SF-36 subscales of physical functioning (P <0.001), pain index (P = 0.002), general health perception (P = 0.02), social functioning (P = 0.02), and the physical component summary (P <0.001). Pairwise comparison among the 4 groups showed that the moderate and low alcohol drinkers had lower severity of fibromyalgia symptoms and better physical QOL than nondrinkers. Conclusions Our study demonstrates that low and moderate

  4. Validity evidence, sensibility and specificity of the severity dimension of the SDSS alcohol dependence scale.

    PubMed

    Vélez-Moreno, Antonio; Lozano, Óscar M; Fernández-Calderón, Fermín; Rojas, Antonio J; Sayans-Jiménez, Pablo; González-Saiz, Francisco; Ramírez López, Juan

    2015-01-01

    Therapeutic success in the treatment of alcohol use disorders highly depends on an appropriate diagnosis. The Substance Dependence Severity Scale –SDSS- is a scale that assesses substance dependence in dimensional terms and that follows the diagnostic criteria established by the international classification systems. The aim of this study is to provide validity evidence for the severity dimension of the alcohol dependence scale of the SDSS comparing it with the Mini International Neuropsychiatric Interview –MINI-, and others variables related to substance use included in the EuropASI. A total of 109 patients admitted for treatment in the Drug Abuse Center Services of Huelva who had used alcohol in the month previous to the interview participated. The SDSS, MINI and EuropASI were administered. The diagnostic capacity of the SDSS was assessed by Receiver Operating Characteristic (ROC) curve analysis, taking the MINI dependence diagnosis as standard. The area under the ROC curve (AUC) was 0.917 (CI=0.867-0.968). The trade-off between parameters was detected for a score of 9, with suitable values of sensitivity and specificity (83.58% and 83.72%). The results support the use of the SDSS for the diagnosis of alcohol dependence and for assessment the severity of dependence. Administration of this scale makes it possible to obtain information, with a single score, on how severe the disorder is and whether the dependence criteria have been met.

  5. Alcohol dependence as a chronic pain disorder

    PubMed Central

    Egli, Mark; Koob, George F.; Edwards, Scott

    2013-01-01

    Dysregulation of pain neurocircuitry and neurochemistry has been increasingly recognized as playing a critical role in a diverse spectrum of diseases including migraine, fibromyalgia, depression, and PTSD. Evidence presented here supports the hypothesis that alcohol dependence is among the pathologies arising from aberrant neurobiological substrates of pain. In this review, we explore the possible influence of alcohol analgesia and hyperalgesia in promoting alcohol misuse and dependence. We examine evidence that neuroanatomical sites involved in the negative emotional states of alcohol dependence also play an important role in pain transmission and may be functionally altered under chronic pain conditions. We also consider possible genetic links between pain transmission and alcohol dependence. We propose an allostatic load model in which episodes of alcohol intoxication and withdrawal, traumatic stressors, and injury are each capable of dysregulating an overlapping set of neural substrates to engender sensory and affective pain states that are integral to alcohol dependence and comorbid conditions such as anxiety, depression, and chronic pain. PMID:22975446

  6. Neuropeptide Y Opposes Alcohol Effects on GABA Release in Amygdala and Blocks the Transition to Alcohol Dependence

    PubMed Central

    Gilpin, Nicholas W.; Misra, Kaushik; Herman, Melissa A.; Cruz, Maureen T.; Koob, George F.; Roberto, Marisa

    2011-01-01

    Background During the transition to alcohol and drug addiction, neuromodulator systems in the extended amygdala are recruited to mediate aspects of withdrawal and relapse via convergence on inhibitory GABA neurons in central amygdala (CeA). Methods This study investigated the role of neuropeptide Y (NPY) in excessive alcohol drinking by making rats dependent on alcohol via alcohol vapor inhalation. This study also utilized intracellular and whole-cell recording techniques to determine the effects of NPY on GABAergic inhibitory transmission in CeA, synaptic mechanisms involved in these NPY effects, and NPY interactions with alcohol in the CeA of alcohol-naïve and alcohol-dependent rats. Results Chronic NPY treatment blocked excessive operant alcohol-reinforced responding associated with alcohol dependence, as well as gradual increases in alcohol responding by intermittently tested non-dependent controls. NPY decreased baseline GABAergic transmission and reversed alcohol-induced enhancement of inhibitory transmission in CeA by suppressing GABA release via actions at presynaptic Y2 receptors. Conclusions These results highlight NPY modulation of GABAergic signaling in central amygdala as a promising pharmacotheraputic target for the treatment of alcoholism. GABA neurons in the CeA likely constitute a major point of convergence for neuromodulator systems recruited during the transition to alcohol dependence. PMID:21459365

  7. Housing Retention in Single-Site Housing First for Chronically Homeless Individuals With Severe Alcohol Problems

    PubMed Central

    Malone, Daniel K.; Clifasefi, Seema L.

    2013-01-01

    Objectives. We studied housing retention and its predictors in the single-site Housing First model. Methods. Participants (n = 111) were chronically homeless people with severe alcohol problems who lived in a single-site Housing First program and participated in a larger nonrandomized controlled trial (2005–2008) conducted in Seattle, Washington. At baseline, participants responded to self-report questionnaires assessing demographic, illness burden, alcohol and other drug use, and psychiatric variables. Housing status was recorded over 2 years. Results. Participants were interested in housing, although a sizable minority did not believe they would be able to maintain abstinence-based housing. Only 23% of participants returned to homelessness during the 2-year follow-up. Commonly cited risk factors—alcohol and other drug use, illness burden, psychiatric symptoms, and homelessness history—did not predict resumed homelessness. Active drinkers were more likely to stay in this housing project than nondrinkers. Conclusions. We found that single-site Housing First programming fills a gap in housing options for chronically homeless people with severe alcohol problems. PMID:24148063

  8. Effectiveness of inpatient withdrawal and residential rehabilitation interventions for alcohol use disorder: A national observational, cohort study in England.

    PubMed

    Eastwood, Brian; Peacock, Amy; Millar, Tim; Jones, Andrew; Knight, Jonathan; Horgan, Patrick; Lowden, Tim; Willey, Peter; Marsden, John

    2018-05-01

    This was a national English observational cohort study to estimate the effectiveness of inpatient withdrawal (IW) and residential rehabilitation (RR) interventions for alcohol use disorder (AUD) using administrative data. All adults commencing IW and/or RR intervention for AUD between April 1, 2014 and March 31, 2015 reported to the National Drug Treatment Monitoring System (n=3812). The primary outcome was successful completion of treatment within 12months of commencement, with no re-presentation (SCNR) in the subsequent six months, analysed by multi-level, mixed effects, multivariable logistic regression. The majority (70%, n=2682) received IW in their index treatment journey; one-quarter (24%, n=915) received RR; 6% (n=215) received both. Of treatment leavers, 59% achieved the SCNR outcome (IW: 57%; RR: 64%; IW/RR: 57%). Positive outcome for IW was associated with older age, being employed, and receiving community-based treatment prior to and subsequent to IW. Patients with housing problems were less likely to achieving the outcome. Positive outcome for RR was associated with paid employment, self/family/peer referral, longer duration of RR treatment, and community-based treatment following discharge. Community-based treatment prior to entering RR, and receiving IW during the same treatment journey as RR, were associated with lower likelihood of SCNR. In this first national effectiveness study of AUD in the English public treatment system for alcohol-use disorders, 59% of patients successfully completed treatment within 12months and did not represent for more treatment within six months. Longer duration of treatment and provision of structured continuing care is associated with better treatment outcomes. Copyright © 2018. Published by Elsevier Inc.

  9. [An examination of the determinants of social withdrawal and affinity for social withdrawal].

    PubMed

    Watanabe, Asami; Matsui, Yutaka; Takatsuka, Yusuke

    2010-12-01

    This study examined the determinants of social withdrawal using data from a survey by the Tokyo Metropolitan Government Office for Youth Affairs and Public Safety (2008). In addition, this study identified young people who showed an affinity for social withdrawal although they were not in a state of withdrawal, and examined the determinants of an affinity for social withdrawal. The results of stepwise discriminant analysis showed that factors such as social phobia, depression, violence, and emotional bonds with family differentiated between the general youth group and the social withdrawal group and the "affinity group". Social phobia, violence, and refusal to be interfered in self-decision making differentiated between the social withdrawal group and the "affinity group". This study shows that an "affinity group" should be cared as well as an actual withdrawal group.

  10. [The effect of palonosetron on rocuronium-induced withdrawal movement].

    PubMed

    Park, Ki-Bum; Jeon, Younghoon; Yi, Junggu; Kim, Ji-Hyun; Chung, Seung-Yeon; Kwak, Kyung-Hwa

    Rocuronium causes pain and withdrawal movement during induction of anesthesia. In this study, palonosetron was investigated to have analgesic effect on the reduction of rocuronium-induced withdrawal movement. 120 patients were randomly assigned to one of three groups to receive either saline, lidocaine 20mg, or palonosetron 0.075mg with a tourniquet applied two minutes before thiopental sodium (5mg.kg -1 ) was given intravenously. After loss of consciousness, rocuronium (0.6mg.kg -1 ) was injected and the withdrawal movement was estimated by 4-point scale in a double-blind manner. The overall incidence of rocuronium withdrawal movement was 50% with lidocaine (p=0.038), 38% with palonosetron (p=0.006) compared with 75% for saline. The incidence of no pain to mild pain was significantly lower in the lidocaine and palonosetron groups (85% and 92% respectively) than in the saline group (58%). However, there was no significant difference in withdrawal movement between the lidocaine and palonosetron groups. There was no severe movement with palonosetron. Pretreatment of palonosetron with venous occlusion may attenuate rocuronium-induced withdrawal movement as effective as the use of lidocaine. It suggested that peripheral action of palonosetron was effective to reduce rocuronium-induced withdrawal movement. Copyright © 2016. Publicado por Elsevier Editora Ltda.

  11. Effect of tofacitinib withdrawal and re-treatment on patient-reported outcomes: results from a Phase 3 study in patients with moderate to severe chronic plaque psoriasis.

    PubMed

    Griffiths, C E M; Vender, R; Sofen, H; Kircik, L; Tan, H; Rottinghaus, S T; Bachinsky, M; Mallbris, L; Mamolo, C

    2017-02-01

    Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. A Phase 3 withdrawal/re-treatment study (NCT01186744; OPT Retreatment) showed tofacitinib re-treatment was effective in patients with chronic plaque psoriasis. To describe the effects of tofacitinib withdrawal/re-treatment on health-related quality of life (HRQoL) and disease symptoms measured by patient-reported outcomes (PROs). The study was divided into initial treatment, treatment withdrawal, and re-treatment periods. Initial treatment: patients were randomized to receive tofacitinib 5 (n = 331) or 10 mg (n = 335) BID for 24 weeks. Treatment withdrawal: patients who achieved both ≥ 75% reduction in Psoriasis Area and Severity Index (PASI) score from baseline and Physician's Global Assessment of 'clear'/'almost clear' at Week (W)24 received placebo (withdrawal) or the previous dose (continuous treatment). Re-treatment: at relapse (> 50% loss of W24 PASI response) or at W40, patients received their initial tofacitinib dose. PROs included: Dermatology Life Quality Index (DLQI), Itch Severity Item (ISI), Short Form-36 (SF-36) and Patient's Global Assessment (PtGA). After initial treatment with tofacitinib 5 and 10 mg BID, substantial and significant improvements were reported for mean DLQI (baseline: 12.6 and 12.6; W24: 5.1 and 2.6) and ISI (baseline: 6.7 and 6.9; W24: 2.9 and 1.6). Patients continuously treated with tofacitinib 5 and 10 mg BID maintained those improvements through Week 56 (DLQI: 3.0 and 2.1; ISI: 2.3 and 1.4). By W40, patients withdrawn from tofacitinib 5 and 10 mg BID showed worsening in DLQI (5.0 and 6.2) and ISI (3.7 and 4.0) scores; improvements were regained upon re-treatment (W56, DLQI: 3.4 and 2.4; ISI: 2.2 and 1.6). Similar results were reported for PtGA and SF-36. Continuous tofacitinib treatment provided sustained improvement in HRQoL and disease symptoms. Patients randomized to treatment withdrawal lost initial improvements. Upon re-treatment, improvements

  12. MDMA attenuates THC withdrawal syndrome in mice.

    PubMed

    Touriño, Clara; Maldonado, Rafael; Valverde, Olga

    2007-07-01

    3, 4-Methylenedioxymethamphetamine (MDMA) and cannabis are widely abused illicit drugs that are frequently consumed in combination. Interactions between these two drugs have been reported in several pharmacological responses observed in animals, such as body temperature, anxiety, cognition, and reward. However, the interaction between MDMA and cannabis in addictive processes such as physical dependence has not been elucidated yet. In this study, the effects of acute and chronic MDMA were evaluated on the behavioral manifestations of Delta(9)-tetrahydrocannabinol (THC) abstinence in mice. THC withdrawal syndrome was precipitated by injecting the cannabinoid antagonist rimonabant (10 mg/kg, i.p.) in mice chronically treated with THC and receiving MDMA (2.5, 5 and 10 mg/kg i.p.) or saline just before the withdrawal induction or chronically after the THC administration. Both chronic and acute MDMA decreased in a dose-dependent manner the severity of THC withdrawal. In vivo microdialysis experiments showed that acute MDMA (5 mg/kg, i.p.) administration increased extracellular serotonin levels in the prefrontal cortex, but not dopamine levels in the nucleus accumbens. Our results also indicate that the attenuation of THC abstinence symptoms was not due to a direct interaction between rimonabant and MDMA nor to the result of the locomotor stimulating effects of MDMA. The modulation of the cannabinoid withdrawal syndrome by acute or chronic MDMA suggests a possible mechanism to explain the associated consumption of these two drugs in humans.

  13. Treatment for amphetamine withdrawal.

    PubMed

    Shoptaw, Steven J; Kao, Uyen; Heinzerling, Keith; Ling, Walter

    2009-04-15

    Few studies examined treatments for amphetamine withdrawal, although it is a common problem among amphetamine users. Its symptoms, in particular intense craving, may be a critical factor leading to relapse to amphetamine use. In clinical practice, medications for cocaine withdrawal are commonly used to manage amphetamine withdrawal although the pharmacodynamic and pharmacokinetic properties of these two illicit substances are different. To assess the effectiveness of pharmacological alone or in combination with psychosocial treatment for amphetamine withdrawals on discontinuation rates, global state, withdrawal symptoms, craving, and other outcomes. MEDLINE (1966 - 2008), CINAHL (1982 - 2008), PsycINFO (1806 - 2008), CENTRAL (Cochrane Library 2008 issue 2), references of obtained articles. All randomised controlled and clinical trials evaluating pharmacological and or psychosocial treatments (alone or combined) for people with amphetamine withdrawal symptoms. Two authors evaluated and extracted data independently. The data were extracted from intention-to-treat analyses. The Relative Risk (RR) with the 95% confidence interval (95% CI) was used to assess dichotomous outcomes. The Weighted Mean Difference (WMD) with 95% CI was used to assess continuous outcomes. Four randomised controlled trials (involving 125 participants) met the inclusion criteria for the review. Two studies found that amineptine significantly reduced discontinuation rates and improved overall clinical presentation, but did not reduce withdrawal symptoms or craving compared to placebo. The benefits of mirtazapine over placebo for reducing amphetamine withdrawal symptoms were not as clear. One study suggested that mirtazapine may reduce hyperarousal and anxiety symptoms associated with amphetamine withdrawal. A more recent study failed to find any benefit of mirtazapine over placebo on retention or on amphetamine withdrawal symptoms. No medication is effective for treatment of amphetamine

  14. Withdrawal Method (Coitus Interruptus)

    MedlinePlus

    Withdrawal method (coitus interruptus) Overview The withdrawal method of contraception, also known as coitus interruptus, is the practice of withdrawing the penis from the vagina and away from a woman's external ...

  15. Alcohol consumption and use of health care services in people with severe mental illness and stressful childhood experiences.

    PubMed

    Schneeberger, Andres R; Huber, Christian G; Seixas, Azizi; Muenzenmaier, Kristina H; Lang, Undine E; Castille, Dorothy; Larkin, Stefan; Link, Bruce G

    2017-01-01

    People who suffer from severe mental illness often present with histories of abuse during childhood. Alcohol use disorders is a common co-morbidity of survivors of childhood abuse and neglect. This study analyzes the effects of stressful childhood experiences, a proxy for trauma, on the frequency of alcohol consumption and the utilization of health care services in a population of people with severe mental illness. There were 111 men (mean age: 35 years) and 72 women (mean age: 40.0 years) with severe mental illness that were recruited from psychiatric outpatient clinics in New York City. The analysis focused on lifetime prevalence of stressful childhood experiences, alcohol consumption, and utilization of health care services over time. The longitudinal data were analyzed over 12 months with a level-2 model (multilevel modeling). Out of the participants, 41.5% reported a history of more than four types of abusive experiences. There were 33.3% that had a DSM-IV diagnosis of alcohol abuse and 27.3% qualified for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of alcohol dependence throughout their lives. Stressful childhood experiences predicted an increased frequency of alcohol consumption over time. People with histories of childhood abuse had more often been to outpatient clinics and 12-step programs, but at the same time showed lower frequency rates of psychiatrist visits and visits to outpatient clinics. Childhood abuse is prevalent in people with severe mental illness and is related to an increased alcohol consumption. Despite an increased need of health care services, affected persons might encounter more barriers to access them.

  16. Anxiety level and correlates in methamphetamine-dependent patients during acute withdrawal.

    PubMed

    Su, Hang; Zhang, Jie; Ren, Wenwei; Xie, Ying; Tao, Jingyan; Zhang, Xiangyang; He, Jincai

    2017-04-01

    Anxiety is often a core element of withdrawal symptoms; however, risk factors associated with anxiety symptoms during the early stage of withdrawal in methamphetamine (METH) users are not well understood. Two hundred ten METH-dependent subjects who had been abstinent for 1 to 7 days were recruited. We used a set of self-administrative questionnaires eliciting information on sociodemographics, detailed drug use history and anxiety. Beck Anxiety Inventory (BAI) was used to measure anxiety symptoms. METH users had a mean BAI score of 6.9; 72 (34.3%) of the study sample had anxiety symptoms during acute METH withdrawal, including 42 (20.0%) with mild anxiety, 25 (11.9%) with moderate anxiety, and 5 (2.4%) with severe anxiety. In addition, gender (female), higher frequency of drug use, and history of polysubstance use were significantly correlated with anxiety symptoms during acute METH withdrawal. Anxiety symptoms appear to be common during the first week of METH abstinence, and several risk factors are identified.

  17. Mental health consequences of exercise withdrawal: A systematic review.

    PubMed

    Weinstein, Ali A; Koehmstedt, Christine; Kop, Willem J

    2017-11-01

    A sedentary lifestyle has been associated with mental health disorders. Many medical conditions result in the cessation of exercise, which may increase the risk of developing mental health problems. The purpose of this article is to systematically review the literature examining the effects of exercise withdrawal on mental health. Literature was searched using PubMed, PsycINFO, and SPORTdiscus for studies that experimentally manipulated the withdrawal of exercise and included mental health as outcome measure. A total of 19 studies met inclusion criteria (total N=689 with 385 individuals participating in an exercise withdrawal condition). Exercise withdrawal consistently resulted in increases in depressive symptoms and anxiety. Other mental health outcomes were investigated infrequently. Severe mental health issues requiring clinical intervention after experimentally controlled exercise withdrawal was rare. Heterogeneity in methods and outcomes was observed, especially in terms of the duration of exercise withdrawal (range 1 to 42days, median=7days), with stronger effects if exercise withdrawal exceeded 2weeks. Experimentally controlled exercise withdrawal has adverse consequences for mental health. These observations in healthy individuals may help to understand the onset of mental health problems in response to acute and chronic medical conditions associated with reduced physical activity. Future research is needed to investigate potential mechanisms explaining the adverse mental health consequences of cessation of exercise that will provide new targets for clinical interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Intracultural accusations of assimilation and alcohol use severity among Hispanic emerging adults: Moderating effects of acculturation, enculturation, and gender.

    PubMed

    Cano, Miguel Ángel

    2016-12-01

    Individuals, including Hispanics, tend to drink most heavily during emerging adulthood (ages 18-25 years old). Research has suggested that intercultural stressors (e.g., ethnic discrimination) may increase levels of alcohol use among Hispanics. However, the relationship between intracultural stressors (e.g., accusations of assimilation-when Hispanics accuse a member of their heritage group of acculturating to U.S. culture) and alcohol use has been examined to a lesser extent. Accordingly, the present study aimed to (a) examine the association between family accusations of assimilation and alcohol use severity; and (b) examine if acculturation domains, enculturation domains, and gender moderated that association. A hierarchical multiple regression and moderation analyses were conducted on a cross-sectional sample of 181 Hispanic emerging adults. Results indicated that higher family accusations of assimilation were associated with higher levels of alcohol use severity (β = .18, p < .05), and all variables entered in the model accounted for ΔR2 = 15.1% of the variance of alcohol use severity. A moderation analysis indicated that higher family accusations of assimilation were associated with higher alcohol use severity among men, but not women. Of the four acculturation/enculturation domains, none had a moderation effect. However, there was a statistically significant three-way interaction among family accusations of assimilation, gender, and affective enculturation. This three-way interaction suggests that among men, higher family accusations of assimilation were associated with higher alcohol use severity at lower levels of affective enculturation. This study addresses a literature gap on intracultural stressors and substance use among Hispanics, and discusses recommendations for future research. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  19. Topiramate in opiate withdrawal.

    PubMed

    Zullino, Daniele F; Cottier, Anne-Claude; Besson, Jacques

    2002-10-01

    The alpha2-adrenergic agonist clonidine is the mainly used drug for the opiate withdrawal. Its efficacy and tolerance in treating withdrawal symptoms is, however, suboptimal. The pharmacological profile of topiramate suggests it could be rather valuable for opiate withdrawal, as there is some evidence that topiramate acts, among others, through inhibition of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors, which play an important role in the withdrawal-induced activation of the locus coeruleus (LC) by glutamate. Three patients undergoing an inpatient opiate detoxification program were treated with topiramate, which achieved a nearly complete control of withdrawal symptoms.

  20. Oxytocin for the treatment of drug and alcohol use disorders.

    PubMed

    Lee, Mary R; Weerts, Elise M

    2016-12-01

    There is growing interest in the use of oxytocin (OT) as a potential treatment for alcohol and other substance-use disorders. OT is a neuropeptide that modulates adaptive processes associated with addiction including reward, tolerance, associative learning, memory, and stress responses. OT exerts its effects through interactions with the hypothalamic-pituitary-adrenal axis and multiple neurotransmitter systems including the dopamine mesolimbic reward and corticotrophin-releasing factor stress systems. The effects of OT on stress systems are of high interest, given the strong link between stress, drug use and relapse, and known dysregulation of hypothalamic-pituitary-adrenal-axis activity associated with substance-use disorders. At the same time, the OT system is itself altered by acute or chronic drug exposure. This review summarizes the preclinical and clinical literature on the OT system and its relevance to drug and alcohol addiction. In addition, findings from recent clinical trials conducted in participants with cocaine, cannabis, or alcohol use disorder are included and evidence that OT may help to normalize blunted stress responses, and attenuate withdrawal-associated hypercortisolism, negative mood, and withdrawal symptoms is summarized.

  1. QT prolongation in the newborn and maternal alcoholism.

    PubMed

    Krasemann, Thomas

    2004-10-01

    I discuss a newborn whose mother is addicted to alcohol. On the third day of life, the newborn was found to have ventricular tachycardia. After spontaneous termination of the abnormal rhythm, the duration of the corrected QT interval was 0.48 s. During the next days, the duration of the interval normalized, and has now remained stable for 5 years. I conclude that the so-called "alcohol withdrawal syndrome of the newborn" might cause postnatal prolongation of the QT interval.

  2. TLR4 Methylation Moderates the Relationship Between Alcohol Use Severity and Gray Matter Loss.

    PubMed

    Karoly, Hollis C; Thayer, Rachel E; Hagerty, Sarah L; Hutchison, Kent E

    2017-09-01

    Alcohol use disorders (AUDs) are associated with decreased gray matter, and neuroinflammation is one mechanism through which alcohol may confer such damage, given that heavy alcohol use may promote neural damage via activation of toll-like receptor 4 (TLR4)-mediated inflammatory signaling cascades. We previously demonstrated that TLR4 is differentially methylated in AUD compared with control subjects, and the present study aims to extend this work by examining whether TLR4 methylation moderates the relationship between alcohol use and gray matter. We examined TLR4 methylation and gray matter thickness in a large sample (N = 707; 441 males) of adults (ages 18-56) reporting a range of AUD severity (mean Alcohol Use Disorders Identification Test score = 13.18; SD = 8.02). We used a series of ordinary least squares multiple regression equations to regress gray matter in four bilateral brain regions (precuneus, lateral orbitofrontal, inferior parietal, and superior temporal) on alcohol use, TLR4 methylation, and their interaction, controlling for demographic, psychological, and other substance use variables. After we corrected for multiple tests, a significant Alcohol × TLR4 Methylation interaction emerged in the equations modeling left precuneus and right inferior parietal gray matter. Follow-up analyses examining the nature of these interactions demonstrated a significant negative association between alcohol and precuneus and inferior parietal gray matter in individuals with low TLR4 methylation, but no relationship between alcohol and gray matter in the high methylation group. These findings suggest that TLR4 methylation may be protective against the damage conferred by alcohol on precuneus and inferior parietal gray matter, thereby implicating TLR4 for further investigation as a possible AUD treatment target.

  3. A pilot study of oxcarbazepine versus acamprosate in alcohol-dependent patients.

    PubMed

    Croissant, Bernhard; Diehl, Alexander; Klein, Oliver; Zambrano, Sergio; Nakovics, Helmut; Heinz, Andreas; Mann, Karl

    2006-04-01

    This pilot study has been designed to collect preliminary data on the use of a new antiepileptic drug in the management of alcoholic patients. Oxcarbazepine (OXC) blocks voltage-sensitive sodium channels. Its metabolite reduces high-voltage-activated calcium currents in striatal and cortical neurons, thus reducing glutamatergic transmission at corticostriatal synapses. This reduction is of interest in the treatment of alcohol dependence, as acamprosate (ACP) modulates NMDA receptors, resulting in an inhibition of glutamatergic transmission. Furthermore, OXC has revealed a mood-stabilizing effect in bipolar affective disorders. We have compared OXC with ACP in relapse prevention in recently withdrawn alcohol-dependent patients. We investigated the efficacy and safety of OXC (vs ACP) by conducting a 24-week randomized, parallel-group, open-label, clinical trial on 30 acutely detoxified alcoholic patients. Survival analyses (Kaplan-Meier) were performed to look for evidence of a longer "survival" of patients receiving OXC. We assessed time to first severe relapse and additional secondary endpoints. After withdrawal, time to severe relapse and time to first consumption of any ethanol by OXC patients were not longer than for ACP patients. Abstinent patients in both study groups showed a significantly lower obsessive compulsive drinking scale-German version (OCDS-G) than relapsed patients. No undesired effects occurred when OXC patients consumed alcohol. Our findings indicate that it could be worthwhile to test relapse prevention using OXC in an adequate sample. While the current sample size clearly limits further conclusions from this pilot study, it is noteworthy that OXC is well tolerated, even when alcohol is on board. Thus, in medication-based relapse prevention, OXC could be a promising alternative for alcoholic patients unable to benefit from ACP or naltrexone or those who have affective liability. OXC certainly merits a larger placebo-controlled trial.

  4. Evidence for a causative role of N-methyl-D-aspartate receptors in an in vitro model of alcohol withdrawal hyperexcitability.

    PubMed

    Thomas, M P; Monaghan, D T; Morrisett, R A

    1998-10-01

    Synaptic mechanisms underlying hyperexcitability due to withdrawal from chronic ethanol exposure were investigated in a hippocampal explant model system using electrophysiological techniques. Whole-cell voltage clamp recordings from CA1 pyramidal cells demonstrated that acute ethanol exposure inhibited N-methyl-D-aspartate receptor (NMDAR)-mediated excitatory postsynaptic currents by over 40%. Chronic ethanol exposure for 6 to 11 days at 35 or 75 mM induced no differences from control explants in the fast component of the population synaptic response (non-NMDAR-mediated). Prolonged field potential recordings (to 10 hr) were used to monitor the withdrawal process in vitro. Ethanol-exposed explants from both 35 and 75 mM groups displayed an increase (60% and 89%, respectively) in the NMDAR-mediated component of synaptic transmission on withdrawal from chronic exposure. Prolonged tonic-clonic electrographic seizure activity was consistently observed after ethanol withdrawal only after the increase in NMDAR function. This hyperexcitability was inhibited by the NMDAR antagonist D-2-amino-5-phosphonovaleric acid and returned once the NMDAR component was reestablished after antagonist washout. In situ hybridization studies suggest that expression of NR2B subunit mRNA may be enhanced in explants after chronic ethanol exposure. No lasting differences were observed in the NMDAR component after acute in vitro ethanol exposure and withdrawal. These data suggest that the occurance of ethanol withdrawal hyperexcitability in this system may be directly dependent on alterations in NMDAR function after chronic exposure. Since this region and others that contain ethanol sensitive NMDARs may serve as epileptic foci, long term alterations in NMDAR function may be expected to generate paroxysmal depolarizing shifts underlying ictal events after withdrawal from ethanol exposure.

  5. Illness severity and self-efficacy as course predictors of DSM-IV alcohol dependence in a multisite clinical sample.

    PubMed

    Langenbucher, J; Sulesund, D; Chung, T; Morgenstern, J

    1996-01-01

    Illness severity and self-efficacy are two constructs of growing interest as predictors of clinical response in alcoholism. Using alternative measures of illness severity (DSM-IV symptom count, Alcohol Dependence Scale, and Addiction Severity Index) and self-efficacy (brief version of the Situational Confidence Questionnaire) rigorously controlled for theoretically important background variables, we studied their unique contribution to multiple indices of relapse, relapse latency, and use of alternative coping behaviors in a large, heterogeneous clinical sample. The Alcohol Dependence Scale contributed to the prediction of 4 of 5 relapse indicators. The SCQ failed to predict relapse behavior or its precursor, coping response. The findings emphasize the predictive validity of severity of dependence as a course specifier and underline the need for more sensitive and externally valid measures of cognitive processes such as self-efficacy for application in future studies of posttreatment behavior.

  6. Confined Selective Withdrawal

    NASA Astrophysics Data System (ADS)

    Evangelio, Alvaro; Campo-Cortes, Francisco; Gordillo, Jose Manuel

    2014-11-01

    It is well known that the controlled production of monodisperse simple and composite emulsions possesses uncountable applications in medicine, pharmacy, materials science and industry. Here we present both experiments and slender-body theory regarding the generation of simple emulsions using a configuration that we have called Confined Selective Withdrawal, since it is an improved configuration of the classical Selective Withdrawal. We consider two different situations, namely, the cases when the outer flow Reynolds number is high and low, respectively. Several geometrical configurations and a wide range of viscosity ratios are analyzed so that the physics behind the phenomenon can be fully understood. In addition, we present both experiments and theory regarding the generation of composite emulsions. This phenomenon is only feasible when the outer flow Reynolds number is low enough. In this case, we propose a more complex theory which requires the simultaneous resolution of two interfaces in order to predict the shape of the jet and the sizes of the drops formed. The excellent agreement between our slender-body approximation and the experimental evidence fully validates our theories.

  7. Corticotropin-Releasing Factor (CRF) Neurocircuitry and Neuropharmacology in Alcohol Drinking.

    PubMed

    Schreiber, Allyson L; Gilpin, Nicholas W

    2018-01-28

    Alcohol use is pervasive in the United States. In the transition from nonhazardous drinking to hazardous drinking and alcohol use disorder, neuroadaptations occur within brain reward and brain stress systems. One brain signaling system that has received much attention in animal models of excessive alcohol drinking and alcohol dependence is corticotropin-releasing factor (CRF). The CRF system is composed of CRF, the urocortins, CRF-binding protein, and two receptors - CRF type 1 and CRF type 2. This review summarizes how acute, binge, and chronic alcohol dysregulates CRF signaling in hypothalamic and extra-hypothalamic brain regions and how this dysregulation may contribute to changes in alcohol reinforcement, excessive alcohol consumption, symptoms of negative affect during withdrawal, and alcohol relapse. In addition, it summarizes clinical work examining CRF type 1 receptor antagonists in humans and discusses why the brain CRF system is still relevant in alcohol research.

  8. Rodent Models of Genetic Contributions to Motivation to Abuse Alcohol

    PubMed Central

    Crabbe, John C.

    2016-01-01

    The distinction between alcohol use (normative) and abuse (unfortunately common) implies dysregulation of motivation directed toward the drug. Genetic contributions to abuse risk are mediated through personality differences, other predispositions to drink excessively, and differences in sensitivity to the acute and chronic consequences of the drug. How to assess motivation in laboratory animals is not straightforward but risk factors for and consequences of alcohol abuse can be modeled with reasonable fidelity in laboratory rodents. Remarkably few rodent studies focus on the genetic contributions to alcohol’s reinforcing value: almost all examine preferential drinking of unflavored alcohol over water. Such studies will likely never avoid the confounding role of taste preferences and most often yield intake levels insufficient to yield a pharmacologically significant blood alcohol level. Genotypes that avoid alcohol probably do so based on pre-ingestive sensory cues; however, post-ingestive consequences are also important. Thus, the quest for improved measures of reinforcing value continues. We have genetic differences aplenty, but still lack evidence that any genotype will readily self-administer alcohol to the devastating extent that many alcoholics will. Encouraging results that are emerging include improved behavioral methods for elevating alcohol intake and inferring alcohol reinforcement, as well as new genetic animal models. Several ingenious assays to index alcohol’s motivational effects have been used extensively. Alcoholic drinking that attempts to prevent or to alleviate withdrawal symptoms has been modeled. Another characteristic of alcoholic drinking is its persistence despite abundant evidence to the drinker of the damaging effects of the excessive drinking on work, relationships, and/or health. Modeling such persistence in rodents has been uncommon to date. New genetic animal models include lines of mice selectively bred for chronic high drinking

  9. Immigration Stress and Alcohol Use Severity Among Recently Immigrated Hispanic Adults: Examining Moderating Effects of Gender, Immigration Status, and Social Support.

    PubMed

    Cano, Miguel Ángel; Sánchez, Mariana; Trepka, Mary Jo; Dillon, Frank R; Sheehan, Diana M; Rojas, Patria; Kanamori, Mariano J; Huang, Hui; Auf, Rehab; De La Rosa, Mario

    2017-03-01

    Identifying and understanding determinants of alcohol use behavior among Hispanic immigrants is an increasingly significant public health concern. Although prior research has examined associations of cultural stressors with alcohol use among Hispanics, few studies have tested these associations among recent adult immigrants. As such, this study aimed to examine (a) the association of immigration stress on alcohol use severity among recently immigrated Hispanic adults (≤ 1 year in the United States) and (b) the moderating effects of gender, immigration status, and social support. A hierarchical multiple regression and moderation analyses were conducted on a sample of 527 participants in South Florida. Results indicated that, after controlling for demographic variables, preimmigration drinking behavior, and dimensions of social support, the association of higher immigration stress with higher alcohol use severity was statistically significant. Moderation analyses indicated that immigration stress had a statistically significant association with alcohol use severity among men, but not women. Also, dimensions of social support consistently reduced the deleterious effect of immigration stress on alcohol use severity. This study adds to the scarce literature on cultural stressors and alcohol use among recent Hispanic immigrants. Findings suggest that it may be important to design gender-specific interventions and that increasing levels of social support may offset the effects of immigration stress on alcohol use. © 2016 Wiley Periodicals, Inc.

  10. Evolution of Wernicke-Korsakoff syndrome in self-neglecting alcoholics: preliminary results of relation with Wernicke-delirium and diabetes mellitus.

    PubMed

    Wijnia, Jan W; van de Wetering, Ben J M; Zwart, Elles; Nieuwenhuis, K Gerrit A; Goossensen, M Anne

    2012-01-01

    We present a descriptive, retrospective study of initial symptoms, comorbidity, and alcohol withdrawal in 73 alcoholic patients with subsequent Korsakoff syndrome. In 25/73 (35%) of the patients the classic triad of Wernicke's encephalopathy with ocular symptoms, ataxia and confusion, was found. In at least 6/35 (17%) of the initial deliria (95% confidence interval: 10-25%) we observed no other underlying causes, thus excluding other somatic causes, medication, (recent) alcohol withdrawal, or intoxication. We suggest that these deliria may have been representing Wernicke's encephalopathy. A high frequency (15%) of diabetics may reflect a contributing factor of diabetes mellitus in the evolution of the Wernicke-Korsakoff syndrome. Copyright © American Academy of Addiction Psychiatry.

  11. Viewpoint: "Alcohol Consumption in Late Adolescence is Associated with an Increased Risk of Severe Liver Disease Later in Life".

    PubMed

    Tamburello, Adriana; Marando, Marco; Bellentani, Stefano

    2018-04-09

    Drinking alcohol during adolescence predispose to severe liver disease in the adult phase. This is the main message of this prospective study. Each daily gram of alcohol men consumed in their youth was linked with a two percent increase in the risk of severe liver disease. No threshold level emerged for liver damage and this is a warning for all the sociologists and politics. New legiferation and educational campaigns addressed to young people, with particular attention to the access to alcohol, prices and advertising are necessary.

  12. Bioactivation of cinnamic alcohol forms several strong skin sensitizers.

    PubMed

    Niklasson, Ida B; Ponting, David J; Luthman, Kristina; Karlberg, Ann-Therese

    2014-04-21

    Cinnamic alcohol is a frequent contact allergen, causing allergic contact dermatitis (ACD) in a substantial number of individuals sensitized from contacts with fragrances. Hence, cinnamic alcohol is one of the constituents in fragrance mix I (FM I) used for screening contact allergy in dermatitis patients. Cinnamic alcohol lacks structural alerts for protein reactivity and must therefore be activated by either air oxidation or bioactivation to be able to act as a sensitizer. In the present study, we explored the bioactivation of cinnamic alcohol using human liver microsomes (HLM), and the potential pathways for these reactions were modeled by in silico (DFT) techniques. Subsequently, the reactivity of cinnamic alcohol and its metabolites toward a model hexapeptide were investigated. In addition to cinnamic aldehyde and cinnamic acid, two highly sensitizing epoxides previously unobserved in studies of bioactivation were detected in the incubations with HLMs. Formation of epoxy cinnamic aldehyde was shown (both by the liver microsomal experiments, in which no depletion of epoxy cinnamic alcohol was observed after initial formation, and by the very high activation energy found for the oxidation thereof by calculations) to proceed via cinnamic aldehyde and not epoxy cinnamic alcohol.

  13. 27 CFR 19.534 - Withdrawals of spirits for use in production of nonbeverage wine and nonbeverage wine products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... use in production of nonbeverage wine and nonbeverage wine products. 19.534 Section 19.534 Alcohol... Withdrawals of spirits for use in production of nonbeverage wine and nonbeverage wine products. Spirits... bonded wine cellar for use in the production of nonbeverage wine and nonbeverage wine products. (Sec. 455...

  14. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall comply...

  15. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall comply...

  16. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall comply...

  17. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall comply...

  18. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall comply...

  19. Treatment for amphetamine withdrawal.

    PubMed

    Srisurapanont, M; Jarusuraisin, N; Kittirattanapaiboon, P

    2001-01-01

    Amphetamine withdrawal has been less studied although it is a common problem with a prevalent rate of 87% among amphetamine users. Its symptoms, in particular intense craving, may be a critical factor leading to relapse of amphetamine use. In clinical practice, treatment for cocaine withdrawal has been recommended for the management of amphetamine withdrawal although the pharmacodynamic and pharmacokinetic properties of these two substances are not the same. To search and determine risks, benefits, and costs of a variety of treatments for the management of amphetamine withdrawal. Electronic searches of MEDLINE (1966 - December 2000), EMBASE (1980 - February 2001), CINAHL (1982 - January 2001) and Cochrane Controlled Trials Register (Cochrane Library 2000 issue 4) were undertaken. References to the articles obtained by any means were searched. All relevant randomised controlled trials (RCTs) and controlled clinical trials (CCTs) were included. Participants were people with amphetamine withdrawal, diagnosed by any set of criteria. Any kinds of biological and psychological treatments both alone and combined were examined. A variety of outcomes, for example, number of treatment responders, score changes, were considered. Two reviewers evaluated and extracted the data independently. The dichotomous data were extracted on an intention-to-treat basis in which the dropouts were assigned as participants with the worst outcomes. The Relative Risk (RR) with the 95% confidence interval (95% CI) was used to assess the dichotomous data. The Weighted Mean Difference (WMD) with 95% CI was used to assessed the continuous data. The results of two studies have shown some benefits of amineptine in the treatment of amphetamine withdrawal. Those benefits can be seen in the respects of discontinuation rate and global state, as measured by Clinical Global Impression Scale. However, no direct benefit of amineptine on amphetamine withdrawal symptoms or craving was shown. The evidence about

  20. Withdrawal: Expanding a Key Addiction Construct

    PubMed Central

    2015-01-01

    Withdrawal is an essential component of classical addiction theory; it is a vital manifestation of dependence and motivates relapse. However, the traditional conceptualization of withdrawal as a cohesive collection of symptoms that emerge during drug deprivation and decline with either the passage of time or reinstatement of drug use, may be inadequate to explain scientific findings or fit with modern theories of addiction. This article expands the current understanding of tobacco withdrawal by examining: (1) withdrawal variability; (2) underlying causes of withdrawal variability, including biological and person factors, environmental influences, and the influence of highly routinized behavioral patterns; (3) new withdrawal symptoms that allow for enhanced characterization of the withdrawal experience; and (4) withdrawal-related cognitive processes. These topics provide guidance regarding the optimal assessment of withdrawal and illustrate the potential impact modern withdrawal conceptualization and assessment could have on identifying treatment targets. PMID:25744958

  1. Characterization of the increased binding of acetaldehyde to red blood cells in alcoholics.

    PubMed

    Hernández-Muñoz, R; Baraona, E; Blacksberg, I; Lieber, C S

    1989-10-01

    Using equilibrium dialysis, we found that acetaldehyde, at the levels commonly occurring after ethanol ingestion, did not bind detectably to plasma proteins, but there was significant binding to red blood cells, more in alcoholics than in nonalcoholics. The binding to red blood cells was inhibited by pyridoxal phosphate and N-ethylmaleimide, suggesting adduction to amino and thiol groups. Binding kinetics were consistent with at least two sites. The one with the highest affinity for acetaldehyde corresponded to hemoglobin. Its affinity and Bmax were not changed in alcoholics, but these binding sites accounted for only 44% of the sites available in the red blood cells of alcoholics and 80% of those in controls. Moreover, this binding was not inhibited by N-ethylmaleimide. There was no detectable binding to red cell ghosts. Nonprotein binding was then assessed by changes in NADH produced by the addition of protein-free fractions of the cells to an alcohol dehydrogenase system in equilibrium; this revealed a second binder of lower affinity, larger capacity and with sensitivity to both inhibitors. This binding (possibly due to thiazolidine formation with cysteine) was enhanced in alcoholics, whose red blood cell cysteine content was doubled. Levels of red blood cell cysteine and acetaldehyde remained high for 2 weeks after withdrawal. Because of the prolonged persistence after withdrawal, these changes may provide new markers of alcoholism.

  2. Brain-derived neurotrophic factor Val66Met polymorphism and alcohol-related phenotypes.

    PubMed

    Nedic, Gordana; Perkovic, Matea Nikolac; Sviglin, Korona Nenadic; Muck-Seler, Dorotea; Borovecki, Fran; Pivac, Nela

    2013-01-10

    Alcoholism is a chronic psychiatric disorder affecting neural pathways that regulate motivation, stress, reward and arousal. Brain-derived neurotrophic factor (BDNF) regulates mood, response to stress and interacts with neurotransmitters and stress systems involved in reward pathways and addiction. Aim of the study was to evaluate the association between a single nucleotide polymorphism (BDNF Val66Met or rs6265) and alcohol related phenotypes in Caucasian patients. In ethnically homogenous Caucasian subjects of the Croatian origin, the BDNF Val66Met genotype distribution was determined in 549 male and 126 female patients with alcohol dependence and in 655 male and 259 female healthy non-alcoholic control subjects. Based on the structured clinical interview, additional detailed clinical interview, the Brown-Goodwin Scale, the Hamilton Rating Scale for Depression and the Clinical Global Impression scores, alcoholic patients were subdivided into those with or without comorbid depression, aggression, delirium tremens, withdrawal syndrome, early/late onset of alcohol abuse, prior suicidal attempt during lifetime, current suicidal behavior, and severity of alcohol dependence. The results showed no significant association between BDNF Val66Met variants and alcohol dependence and/or any of the alcohol related phenotypes in either Caucasian women, or men, with alcohol dependence. There are few limitations of the study. The overall study sample size was large (N=1589) but not well-powered to detect differences in BDNF Val66Met genotype distribution between studied groups. Healthy control women were older than female alcoholic patients. Only one BDNF polymorphism (rs6265) was studied. In conclusion, these data do not support the view that BDNF Val66Met polymorphism correlates with the specific alcohol related phenotypes in ethnically homogenous medication-free Caucasian subjects with alcohol dependence. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. 5' UTR polymorphism of dopamine receptor D1 (DRD1) associated with severity and temperament of alcoholism.

    PubMed

    Kim, Dai-Jin; Park, Byung Lae; Yoon, Sujung; Lee, Hae-Kook; Joe, Keun-Ho; Cheon, Young-Hoon; Gwon, Do-Hoon; Cho, Sung-Nam; Lee, Hye Won; NamGung, Suk; Shin, Hyoung Doo

    2007-06-15

    Multiple dopamine receptors in the dopaminergic system may be prime candidates for genetic influence on alcohol abuse and dependence due to their involvement in reward and reinforcing mechanisms. Genetic polymorphisms in dopamine receptor genes are believed to influence the development and/or severity of alcoholism. To examine the genetic effects of the Dopamine Receptor D1 (DRD) gene family (DRD1-DRD5) in the Korean population, 11 polymorphisms in the DRD gene family were genotyped and analyzed in 535 alcohol-dependent subjects and 273 population controls. Although none of the polymorphisms of DRD1-5 genes were found to be associated with the risk of alcoholism, one 5' UTR polymorphism in the DRD1 (DRD1-48A>G) gene was significantly associated with severity of alcohol-related problem, as measured by the Alcohol Use Disorders Identification Test (AUDIT) in a gene dose-dependent manner, i.e., 24.37 (+/-8.19) among patients with -48A/A genotype, 22.37 (+/-9.49) among those with -48A/G genotype, and 17.38 (+/-8.28) among those with -48G/G genotype (P=0.002). The genetic effects of DRD1-48A>G were further analyzed with other phenotypes among alcohol-dependent subjects. Interestingly, the DRD1-48A>A genotype was also found to be associated with novelty seeking (NC), harm avoidance (HA), and persistence (P) (P =0.01, 0.02, and 0.003, respectively). The information derived from this study could be valuable for understanding the genetic factors involved in alcoholic phenotypes and genetic distribution of the DRD gene family, and could facilitate further investigation in other ethnic groups.

  4. Changes in Withdrawal and Craving Scores in Participants Undergoing Opioid Detoxification Utilizing Ibogaine.

    PubMed

    Malcolm, Benjamin J; Polanco, Martin; Barsuglia, Joseph P

    2018-04-02

    Opioid use disorder (OUD) is currently an epidemic in the United States (US) and ibogaine is reported to have the ability to interrupt opioid addiction by simultaneously mitigating withdrawal and craving symptoms. This study examined opioid withdrawal and drug craving scores in 50 participants with OUD undergoing a week-long detoxification treatment protocol with ibogaine. The Addiction Severity Index (ASI) was used for baseline characterization of participants' OUD. Clinical Opioid Withdrawal Scale (COWS), Subjective Opioid Withdrawal Scale (SOWS), and Brief Substance Craving Scale (BSCS) scores were collected at 48 and 24 hours prior to ibogaine administration, as well as 24 and 48 hours after ibogaine administration. At 48 hours following ibogaine administration, withdrawal and craving scores were significantly lowered in comparison to baseline: 78% of patients did not exhibit objective clinical signs of opioid withdrawal, 79% reported minimal cravings for opioids, and 68% reported subjective withdrawal symptoms in the mild range. Ibogaine appears to facilitate opioid detoxification by reducing opioid withdrawal and craving in participants with OUD. These results warrant further research using rigorous controlled trials.

  5. Gender differences in self-reported withdrawal symptoms and reducing or quitting smoking three years later: A prospective, longitudinal examination of U.S. adults

    PubMed Central

    Weinberger, Andrea H.; Platt, Jonathan; Shuter, Jonathan; Goodwin, Renee D.

    2016-01-01

    Background Little is known about gender differences in withdrawal symptoms among smokers in the community. This study used longitudinal epidemiologic data to examine gender differences in current smokers’ report of withdrawal symptoms during past quit attempts and the relationship between withdrawal symptoms and the odds of reducing or quitting smoking three years later. Methods Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; Wave 1, 2001–2001, n=43,093; Wave 2, 2004–2005, n=34,653). Analyses were conducted on respondents who reported current daily cigarette smoking at Wave 1 (n=6,911). Withdrawal symptoms during past quit attempts were assessed at Wave 1. Current smoking status was assessed at Wave 2. Results Wave 1 current smoking women, compared to men, were more likely to endorse any withdrawal symptoms, withdrawal-related discomfort, and withdrawal-related relapse (ps<0.0001). Women endorsed a greater number of withdrawal symptoms than men (M=2.37, SE=0.05 versus M=1.78, SE=0.04; p<0.0001). The odds of reducing and quitting smoking were significantly lower for respondents who reported any Wave 1 withdrawal symptoms, withdrawal-related discomfort, and withdrawal-related relapse. These relationships did not differ for women versus men. Among men, the odds of reducing smoking at Wave 2 decreased significantly with each cumulative withdrawal symptom compared to women (β interaction= 0.87; p=0.01). Conclusions Women were more likely to report withdrawal while the relationship between withdrawal symptoms and decreased likelihood of reducing smoking was stronger in men. Identifying gender differences in withdrawal can help develop strategies to help reduce withdrawal for both men and women. PMID:27350655

  6. Effects of alcohol on c-Myc protein in the brain

    PubMed Central

    Akinyeke, Tunde; Weber, Sydney J; Davenport, April T; Baker, Erich J; Daunais, James B; Raber, Jacob

    2018-01-01

    Alcoholism is a disorder categorized by significant impairment that is directly related to persistent and extreme use of alcohol. The effects of alcoholism on c-Myc protein expression in the brain have been scarcely studied. This is the first study to investigate the role of different characteristics of alcoholism in c-Myc protein levels in the brain. We analyzed c-Myc protein in the hypothalamus and amygdala from four different animal models of alcohol abuse. c-Myc protein was increased following alcohol exposure in acute, chronic and withdrawal models. We also observed increases in c-Myc protein exposure in animals that are genetically predisposed to alcohol and methamphetamine abuse. Lastly, c-Myc protein was increased in animals that were acutely exposed to methamphetamine when compared to control treated animals. These results suggest that in substance abuse c-Myc plays an important role in the brain’s response. PMID:27832980

  7. Alcoholism: genes and mechanisms.

    PubMed

    Oroszi, Gabor; Goldman, David

    2004-12-01

    Alcoholism is a chronic relapsing/remitting disease that is frequently unrecognized and untreated, in part because of the partial efficacy of treatment. Only approximately one-third of patients remain abstinent and one-third have fully relapsed 1 year after withdrawal from alcohol, with treated patients doing substantially better than untreated [1]. The partial effectiveness of strategies for prevention and treatment, and variation in clinical course and side effects, represent a challenge and an opportunity to better understand the neurobiology of addiction. The strong heritability of alcoholism suggests the existence of inherited functional variants of genes that alter the metabolism of alcohol and variants of other genes that alter the neurobiologies of reward, executive cognitive function, anxiety/dysphoria, and neuronal plasticity. Each of these neurobiologies has been identified as a critical domain in the addictions. Functional alleles that alter alcoholism-related intermediate phenotypes include common alcohol dehydrogenase 1B and aldehyde dehydrogenase 2 variants that cause the aversive flushing reaction; catechol-O-methyltransferase (COMT) Val158Met leading to differences in three aspects of neurobiology: executive cognitive function, stress/anxiety response, and opioid function; opioid receptor micro1 (OPRM1) Asn40Asp, which may serve as a gatekeeper molecule in the action of naltrexone, a drug used in alcoholism treatment; and HTTLPR, which alters serotonin transporter function and appears to affect stress response and anxiety/dysphoria, which are factors relevant to initial vulnerability, the process of addiction, and relapse.

  8. Daily marijuana users with past alcohol problems increase alcohol consumption during marijuana abstinence.

    PubMed

    Peters, Erica N; Hughes, John R

    2010-01-15

    Drug abuse treatment programs typically recommend complete abstinence because of a fear that clients who stop use of one drug will substitute another. A within-subjects study investigated whether consumption of alcohol and other substances changes during marijuana abstinence. Twenty-eight daily marijuana users who were not trying to stop or reduce their marijuana consumption completed an 8-day baseline period in which they used marijuana and other drugs as usual, a 13-day marijuana abstinence period, and a 7-day return-to-baseline period. Participants provided self-report of substance use daily and submitted urine samples twice weekly to verify marijuana abstinence. A diagnosis of past alcohol abuse or dependence significantly moderated the alcohol increase from baseline to marijuana abstinence (p<0.01), such that individuals with this diagnosis significantly increased alcohol use (52% increase) but those without this history did not (3% increase). Increases in marijuana withdrawal discomfort scores and alcohol craving scores from baseline to marijuana abstinence significantly and positively correlated with increases in alcohol use. Increases in cigarettes, caffeine, and non-marijuana illicit drugs did not occur. This study provides empirical validation of drug substitution in a subgroup of daily marijuana users, but results need to be replicated in individuals who seek treatment for marijuana problems. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

  9. Withdrawal: Expanding a Key Addiction Construct.

    PubMed

    Piper, Megan E

    2015-12-01

    Withdrawal is an essential component of classical addiction theory; it is a vital manifestation of dependence and motivates relapse. However, the traditional conceptualization of withdrawal as a cohesive collection of symptoms that emerge during drug deprivation and decline with either the passage of time or reinstatement of drug use, may be inadequate to explain scientific findings or fit with modern theories of addiction. This article expands the current understanding of tobacco withdrawal by examining: (1) withdrawal variability; (2) underlying causes of withdrawal variability, including biological and person factors, environmental influences, and the influence of highly routinized behavioral patterns; (3) new withdrawal symptoms that allow for enhanced characterization of the withdrawal experience; and (4) withdrawal-related cognitive processes. These topics provide guidance regarding the optimal assessment of withdrawal and illustrate the potential impact modern withdrawal conceptualization and assessment could have on identifying treatment targets. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Pharmacological therapies for management of opium withdrawal.

    PubMed

    Rahimi-Movaghar, Afarin; Gholami, Jaleh; Amato, Laura; Hoseinie, Leila; Yousefi-Nooraie, Reza; Amin-Esmaeili, Masoumeh

    2018-06-21

    Pharmacologic therapies for management of heroin withdrawal have been studied and reviewed widely. Opium dependence is generally associated with less severe dependence and milder withdrawal symptoms than heroin. The evidence on withdrawal management of heroin might therefore not be exactly applicable for opium. To assess the effectiveness and safety of various pharmacologic therapies for the management of the acute phase of opium withdrawal. We searched the following sources up to September 2017: CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, regional and national databases (IMEMR, Iranmedex, and IranPsych), main electronic sources of ongoing trials, and reference lists of all relevant papers. In addition, we contacted known investigators to obtain missing data or incomplete trials. Controlled clinical trials and randomised controlled trials on pharmacological therapies, compared with no intervention, placebo, other pharmacologic treatments, different doses of the same drug, and psychosocial intervention, to manage acute withdrawal from opium in a maximum duration of 30 days. We used the standard methodological procedures expected by Cochrane. We included 13 trials involving 1096 participants. No pooled analysis was possible. Studies were carried out in three countries, Iran, India, and Thailand, in outpatient and inpatient settings. The quality of the evidence was generally very low.When the mean of withdrawal symptoms was provided for several days, we mainly focused on day 3. The reason for this was that the highest severity of opium withdrawal is in the second to fourth day.Comparing different pharmacological treatments with each other, clonidine was twice as good as methadone for completion of treatment (risk ratio (RR) 2.01, 95% confidence interval (CI) 1.69 to 2.38; 361 participants, 1 study, low-quality evidence). All the other results showed no differences between the considered drugs: baclofen versus clonidine (RR 1.06, 95% CI 0.63 to 1.80; 66 participants, 1

  11. Alcohol and Caffeine: The Perfect Storm

    PubMed Central

    O'Brien, Mary Claire

    2011-01-01

    Although it is widely believed that caffeine antagonizes the intoxicating effects of alcohol, the molecular mechanisms underlying their interaction are incompletely understood. It is known that both caffeine and alcohol alter adenosine neurotransmission, but the relationship is complex, and may be dose dependent. In this article, we review the available literature on combining caffeine and alcohol. Ethical constraints prohibit laboratory studies that would mimic the high levels of alcohol intoxication achieved by many young people in real-world settings, with or without the addition of caffeine. We propose a possible neurochemical mechanism for the increase in alcohol consumption and alcohol-related consequences that have been observed in persons who simultaneously consume caffeine. Caffeine is a nonselective adenosine receptor antagonist. During acute alcohol intake, caffeine antagonizes the “unwanted” effects of alcohol by blocking the adenosine A1 receptors that mediate alcohol's somnogenic and ataxic effects. The A1 receptor–mediated “unwanted” anxiogenic effects of caffeine may be ameliorated by alcohol-induced increase in the extracellular concentration of adenosine. Moreover, by means of interactions between adenosine A2A and dopamine D2 receptors, caffeine-mediated blockade of adenosine A2A receptors can potentiate the effects of alcohol-induced dopamine release. Chronic alcohol intake decreases adenosine tone. Caffeine may provide a “treatment” for the withdrawal effects of alcohol by blocking the effects of upregulated A1 receptors. Finally, blockade of A2A receptors by caffeine may contribute to the reinforcing effects of alcohol. PMID:24761263

  12. Object relations, reality testing, and social withdrawal in schizophrenia and bipolar disorder.

    PubMed

    Hansen, Charlotte Fredslund; Torgalsbøen, Anne-Kari; Røssberg, Jan Ivar; Romm, Kristin Lie; Andreassen, Ole Andreas; Bell, Morris D; Melle, Ingrid

    2013-03-01

    In this study, we investigated the relationships between observed social withdrawal (Positive and Negative Syndrome Scale [PANSS] Passive Social Withdrawal and PANSS Active Social Avoidance), subjectively experienced social withdrawal (Social Functioning Scale [SFS] Withdrawal and SFS Interpersonal Behavior), and their associations to the underlying psychological patterns of Object Relations and Reality Testing. Patients with schizophrenia (n = 55) and bipolar disorder (n = 51) from the ongoing Thematically Organized Psychosis project, Oslo University Hospital, Norway, were evaluated using the Bell Object Relations and Reality Testing Inventory, the PANSS, and the SFS. Object relations and reality testing subscales related differentially to PANSS Passive Social Withdrawal and PANSS Active Social Avoidance. These two measures, together with the level of alienation, explained a significant amount of variance in self-experienced social dysfunction. Findings reveal the multidimensional nature of social dysfunction in severe mental disorders.

  13. Alcohol-Use Disorders in the Critically Ill Patient

    PubMed Central

    Jones, Drew G.; Sessler, Curtis N.; Zilberberg, Marya D.; Weaver, Michael F.

    2010-01-01

    Alcohol abuse and dependence, referred to as alcohol-use disorders (AUDs), affect 76.3 million people worldwide and account for 1.8 million deaths per year. AUDs affect 18.3 million Americans (7.3% of the population), and up to 40% of hospitalized patients have AUDs. This review discusses the development and progression of critical illness in patients with AUDs. In contrast to acute intoxication, AUDs have been linked to increased severity of illness in a number of studies. In particular, surgical patients with AUDs experience higher rates of postoperative hemorrhage, cardiac complications, sepsis, and need for repeat surgery. Outcomes from trauma are worse for patients with chronic alcohol abuse, whereas burn patients who are acutely intoxicated may not have worse outcomes. AUDs are linked to not only a higher likelihood of community-acquired pneumonia and sepsis but also a higher severity of illness and higher rates of nosocomial pneumonia and sepsis. The management of sedation in patients with AUDs may be particularly challenging because of the increased need for sedatives and opioids and the difficulty in diagnosing withdrawal syndrome. The health-care provider also must be watchful for the development of dangerous agitation and violence, as these problems are not uncommonly seen in hospital ICUs. Despite studies showing that up to 40% of hospitalized patients have AUDs, relatively few guidelines exist on the specific management of the critically ill patient with AUDs. AUDs are underdiagnosed, and a first step to improving patient outcomes may lie in systematically and accurately identifying AUDs. PMID:20923804

  14. Alcohol education revisited: exploring how much time we devote to alcohol education in the nursing curriculum.

    PubMed

    Cund, Audrey

    2013-01-01

    This study examines student nurses knowledge, attitudes and educational preparation to work with patients who misuse alcohol. The study begins to quantify how much time is devoted to alcohol education at one Scottish University. The study modified the Short Alcohol Attitudes Problem Perception Questionnaire (SAAPPQ) and incorporated three case vignettes to examine the student nurses knowledge, attitudes and experience of working with patients who have an alcohol problem. The questionnaire was hand delivered to a convenience sample of third year nursing students. The results show that the student nurses exhibit positive attitudes and beliefs about working with patients who have an alcohol misuse problem. A series of significant associations was found between the adult nursing cohort and their ability to include a comprehensive alcohol history in their nursing assessments (χ(2) = 19.82, df = 4, p < 0.0005); recognise signs of acute alcohol withdrawal (χ(2) = 52.26, df = 16, p < 0.000); and the psychological signs associated with alcohol misuse (χ(2) = 41.81, df = 16, p < 0.000). A baseline figure of 2.5 h of alcohol education is noted at this university. Alcohol education strongly features in three out of the five nursing programmes surveyed. Nurse education needs to focus on strategies that extend to teaching nurses how to respond, provide brief interventions and identify when to refer the patient for specialist intervention. These approaches should be universal to all areas of nursing practice. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Caffeine Withdrawal and Dependence: A Convenience Survey Among Addiction Professionals.

    PubMed

    Budney, Alan J; Brown, Pamela C; Griffiths, Roland R; Hughes, John R; Juliano, Laura M

    2013-06-01

    Caffeine withdrawal was included in the research appendix of the DSM-IV to encourage additional research to assist with determining its status for the next version of the manual. Caffeine dependence was not included because of a lack of empirical research at the time of publication. This study assessed the beliefs of addiction professionals about the clinical importance of caffeine withdrawal and dependence. A 6-item survey was developed and delivered electronically to the members of six professional organizations that focus on addiction. Open-ended comments were also solicited. Five hundred members responded. The majority (95%) thought that cessation of caffeine could produce a withdrawal syndrome, and that caffeine withdrawal can have clinical importance (73%); however, only half (48%) thought that caffeine withdrawal should be included in the Diagnostic and Statistical Manual of Mental Disorders (DSM). A majority (58%) believed that some people develop caffeine dependence; however, only 44% indicated that it should be in the DSM. Comments suggested that trepidation about inclusion of caffeine diagnoses was due to the concerns about the field of psychiatry being criticized for including common disorders with a relatively low clinical severity. Others, however, expressed an urgent need to take caffeine-related problems more seriously. The majority of addiction professionals believe that caffeine withdrawal and dependence disorders exist and are clinically important; however, these professionals are divided in whether caffeine withdrawal and dependence should be included in DSM. Wider dissemination of the extant literature on caffeine withdrawal and additional research on caffeine dependence will be needed to provide additional guidance to policymakers and healthcare workers.

  16. Time-course of the DSM-5 cannabis withdrawal symptoms in poly-substance abusers

    PubMed Central

    2013-01-01

    Background Evidence is accumulating that a cannabis withdrawal syndrome is common, of clinical significance, and has a clear time course. Up till now, very limited data exist on the cannabis withdrawal symptoms in patients with co-morbid substance use disorders, other than cannabis use and tobacco use. Methods Symptoms of withdrawal were assessed through patient self-reports during detoxification in Danish residential rehabilitation centers. Patients (n = 90) completed booklets three times during their first month at the treatment centre. Self-reported withdrawal symptoms was rated using the DSM-5 Withdrawal Symptom Check List with withdrawal symptoms from all classes of substances, with no indication that the described symptoms should be attributed to withdrawal. Self-reported time since last use of cannabis was used as a predictor of cannabis withdrawal severity. Results With the exception of loss of appetite, time since last use of cannabis was associated with all types of withdrawal symptoms listed in the DSM-5. Only four of 19 symptoms intended to measure withdrawal from other substances were related to time since last use of cannabis, including vivid, unpleasant dreams. Conclusions The findings yield strong support to the notion of a cannabis withdrawal syndrome, and gives further evidence for the inclusion of the criterion of vivid, unpleasant dreams. Further, the findings speak against the significance of demand characteristics in determining the course of the symptoms of cannabis withdrawal. PMID:24118963

  17. High-dose benzodiazepine dependence: a qualitative study of patients' perception on cessation and withdrawal.

    PubMed

    Liebrenz, Michael; Gehring, Marie-Therese; Buadze, Anna; Caflisch, Carlo

    2015-05-13

    Benzodiazepine withdrawal syndrome has been reported following attempts to withdraw even from low or therapeutic doses and has been compared to barbiturate and alcohol withdrawal. This experience is known to deter patients from future cessation attempts. Research on other psychotropic substances shows that the reasons and motivations for withdrawal attempts - as well as the experiences surrounding those attempts - at least partially predict future efforts at discontinuation as well as relapse. We therefore aimed to qualitatively explore what motivates patients to discontinue this medication as well as to examine their experiences surrounding previous and current withdrawal attempts and treatment interventions in order to positively influence future help-seeking behavior and compliance. To understand these patients better, we conducted a series of 41 unstructured, narrative, in-depth interviews among adult Swiss patients with a long-term dependent use of benzodiazepines in doses equivalent to more than 40 mg diazepam per day and/or otherwise problematic use (mixing benzodiazepines, escalating dosage, recreational use or illegal purchase). Mayring's qualitative content analysis was used to evaluate findings. These high-dose benzodiazepine-dependent patients decision to change consumption patterns were affected by health concerns, the feeling of being addicted and social factors. Discontinuation attempts were frequent and not very successful with fast relapse. Withdrawal was perceived to be a difficult, complicated, and highly unpredictable process. The first attempt at withdrawal occurred at home and typically felt better than at the clinic. Inpatient treatment was believed to be more effective with long term treatment (approaches) than short term. Patients preferred gradual reduction of usage to abrupt cessation (and had experienced both). While no clear preferences for withdrawal were found for benzodiazepines with specific pharmacokinetic properties, participants

  18. Association between alcoholism and the genetic polymorphisms of the GABAA receptor genes on chromosome 5q33-34 in Korean population.

    PubMed

    Park, Chul-Soo; Park, So-Young; Lee, Chul-Soon; Sohn, Jin-Wook; Hahn, Gyu-Hee; Kim, Bong-Jo

    2006-06-01

    Family, twin, and adoption studies have demonstrated that genes play an important role in the development of alcoholism. We investigated the association between alcoholism and the genetic polymorphisms of the GABAA receptor genes on chromosome 5q33-34 in Korean population. The genotype of the GABAA receptor gene polymorphisms were determined by performing polymerase chain reaction genotyping for 172 normal controls and 162 male alcoholics who are hospitalized in alcoholism treatment institute. We found a significant association between the genetic polymorphisms of the GABAA alpha1 and GABAA alpha6 receptor gene and alcoholism. The GG genotype of the GABAA alpha1 receptor gene was associated with the onset age of alcoholism and alcohol withdrawal symptoms, and a high score on the Korean version of the ADS. However, there was no association between the genetic polymorphisms of the GABAA beta2 and gamma2 receptor gene and alcoholisms. Our finding suggest that genetic polymorphisms of the GABAA alpha1 and GABAA alpha6 receptor gene may be associated with the development of alcoholism and that the GG genotype of the GABAA alpha1 receptor gene play an important role in the development of the early onset and the severe type of alcoholism.

  19. [Clinical Practice Guide for Early Detection, Diagnosis and Treatment of the Acute Intoxication Phase in Patients with Alcohol Abuse or Dependence: Part II: Evaluation and Management of Patients with Acute Alcohol Intoxication].

    PubMed

    de la Espriella Guerrero, Ricardo; de la Hoz Bradford, Ana María; Zárate, Alina Uribe-Holguín; Lee, Patricia Rodríguez; Menéndez, Miguel Cote; Rentería, Ana María Cano; Hernández, Delia Cristina; Cardeño, Carlos; Barré, Michelle Cortés; Kunzel, Gabriel Hernández; Gómez-Restrepo, Carlos

    2012-12-01

    Worldwide, alcohol is the second most-used psychotropic substance and the third risk factor for early death and disability. Its noxious use is a world public health problem given its personal, labor, family, economic and social impact. The identification of acute alcohol intoxication is extremely important, as well as the alcohol withdrawal syndrome and its complications, such as delirium tremens and Wernicke's encephalopathy in order to grant a timely treatment for those patients. This article introduces the evidence found so as to face and treat these clinic manifestations. Systematic revision of the evidence available together with an evaluation of pertinent guidelines found in literature so as to decide whether to adopt or adapt the existing recommendation for each question or to develop de novo recommendations. For de novo recommendations as well as those adapted, it was carried out an evidence synthesis, together with evidence tables and formulation of recommendations based on the evidence. Evidence was found and recommendations were made for the diagnosis and treatment of acute alcohol intoxication, withdrawal syndrome, delirium tremens and Wernicke's encephalopathy. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  20. Strategies to avoid opiate withdrawal: implications for HCV and HIV risks.

    PubMed

    Mateu-Gelabert, Pedro; Sandoval, Milagros; Meylakhs, Peter; Wendel, Travis; Friedman, Samuel R

    2010-05-01

    Research on heroin withdrawal has primarily been done clinically, thus focussing on symptom severity, physiological manifestations, and how withdrawal impairs normal functioning. However, there is little scientific knowledge on how heroin withdrawal affects injection behaviour. This paper explores how withdrawal episodes heighten unsafe injection practices and how some long-term injectors manage such risks. We interviewed 32 injection drug users in New York City who had been injecting drugs for 8-15 years (21 HIV and HCV uninfected; 3 HIV and HCV infected; and 8 singly infected with HCV). We used in-depth life history interviews to inquire about IDUs' life history, injection practices and drug use behaviour over time. Analysis used grounded theory techniques. Withdrawal can enhance risk by undermining IDUs' willingness to inject safely; increasing the likelihood of attending risky settings; raising the number of injection partners; and seeking ad hoc partners for drug or needle sharing. Some IDUs have developed practices to cope with withdrawal and avoid risky practices (examples include carrying clean needles to shooting galleries and sniffing rather than injecting). Strategies to avoid withdrawal include back up methods, resorting to credit, collaborating with others, regimenting drug intake, balancing drug intake with money available, and/or resorting to treatment. Withdrawal periods can heighten risky injection practices. Some IDUs have applied strategies to avoid withdrawal or used practices to cope without engaging in risky practices. These behaviours might in turn help IDUs prevent an infection with hepatitis C or HIV. Copyright 2009 Elsevier B.V. All rights reserved.

  1. Development of the caffeine withdrawal symptom questionnaire: caffeine withdrawal symptoms cluster into 7 factors.

    PubMed

    Juliano, Laura M; Huntley, Edward D; Harrell, Paul T; Westerman, Ashley T

    2012-08-01

    Habitual caffeine consumers who abstain from caffeine experience withdrawal symptoms such as headache, fatigue, difficulty concentrating, mood disturbances, and flu-like symptoms (Juliano and Griffiths, 2004). The caffeine withdrawal syndrome has been documented across many experimental studies; however, little is known about how withdrawal symptoms co-vary during a discrete episode. Furthermore, a validated measure of caffeine withdrawal is lacking. To develop, evaluate, and reduce a 23-item measure of caffeine withdrawal symptoms; the Caffeine Withdrawal Symptom Questionnaire (CWSQ), to a set of composite variables. Caffeine consumers (N=213) completed the CWSQ after 16h of caffeine abstinence. A subset of participants also completed the CWSQ during a preceding baseline period and/or after double-blind consumption of caffeinated coffee. Principal components analysis resulted in a solution comprised of 7-factors: (1) Fatigue/drowsiness; (2) Low alertness/difficulty concentrating; (3) Mood disturbances; (4) Low sociability/motivation to work; (5) Nausea/upset stomach; (6) Flu-like feelings; and (7) Headache. With the exception of nausea/upset stomach, the CWSQ total score and individual composite scores were significantly greater during caffeine abstinence relative to both baseline and double-blind consumption of caffeinated coffee, thereby demonstrating sensitivity of the measure. Compared to non-daily coffee consumers, daily consumers had greater increases in total withdrawal, fatigue/drowsiness, low alertness/difficulty concentrating, mood disturbances, and headache. Future directions include replication, assessment on a clinical population, and further examination of psychometric properties of the CWSQ. The CWSQ should facilitate the assessment and diagnosis of caffeine withdrawal and increase our knowledge of the caffeine withdrawal syndrome. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. Behavioral Analysis of Chronic Alcoholism in Four Women

    ERIC Educational Resources Information Center

    Tracey, Dorothy A.; Nathan, Peter E.

    1976-01-01

    The behavior of four female alcoholics was observed over a 22-day period. A 12-day drinking period was preceded by a 6-day predrinking baseline assessment period and followed by a 4-day postdrinking withdrawal phase. Points were earned for operant responding at a button-pressing task. No changes in psychopathology were noted during drinking.…

  3. Severe diffuse axon injury in chronic alcoholic rat medulla oblongata following a concussion blow.

    PubMed

    Luo, Jianming; Chen, Guang; Wei, Lai; Qian, Hong; Lai, Xiaoping; Wang, Dian; Lv, Junyao; Yu, Xiaojun

    2014-01-01

    We investigated the axonal morphological changes and expression of both tau protein and β-APP following concussion to the medulla oblongata, in a rat model of chronic alcoholism. Fifty-nine male Sprague-Dawley rats were randomly divided into EtOH, EtOH-TBI and control groups (water group, water-TBI group). To establish chronic alcoholic rats, rats were intragastrically given edible spirituous liquor twice daily. Rats also received a blow on the occipital tuberosity with an iron pendulum. Morphological changes and expression of tau and β-APP proteins in the medulla oblongata were examined. (a) Nerve fibre thickening and twisting were observed in alcoholic rats, with nerve fibre changes becoming more significant following a concussion blow, which leads to some nerve fibres fracturing. (b) Transmission electron microscopy revealed that the nerve fibre myelin became loosened and displayed lamellar separation, which became more significant following concussion. (c) The integral optical density (IOD) sum value of β-APP of the EtOH-TBI group was lower than that in the EtOH group (P < 0.05); the Tau IOD sum value of the EtOH-TBI group was higher than that in the EtOH group (P < 0.05). (a) Chronic alcoholism caused nerve fibre and neuronal morphology damage in the rat medulla oblongata, with structural damage becoming more significant following concussion. (b) Concussion changed the expression of β-APP and tau protein in chronic alcoholic rat medulla oblongata, suggesting that chronic alcoholism can lead to severe axonal injury following a concussion blow. (c) The effect of chronic alcoholism may be synergistic the concussion blow to promote animal injury and death.

  4. The Effect of Blood Alcohol Level and Pre-Injury Chronic Alcohol Use on Outcome from Severe Traumatic Brain Injury in Hispanics, Anglo-Caucasians, and African Americans

    PubMed Central

    O’Dell, Keira M.; Hannay, H. Julia; Biney, Fedora O.; Robertson, Claudia S.; Tian, T. Siva

    2012-01-01

    Objective To examine a) ethnic differences in blood alcohol level (BAL) and pre-injury chronic alcohol use (PI-ETOH) within a severe closed head injury (CHI) sample, and b) the main and interaction effects of BAL, PI-ETOH, and ethnicity on functional outcome following severe CHI. Participants 434 Hispanic, Anglo-Caucasian, and African American individuals with severe CHI. Design Retrospective cohort study. Setting Consecutive admissions to a level one trauma center. Main measures BAL upon admission to the trauma center was collected for each patient. Additional information regarding PI-ETOH was collected in a subset of patients (N=116). Functional outcome was measured using the Disability Rating Scale (DRS) at 6 months post-injury. Results A one-way ANOVA revealed ethnic differences in mean BAL. Hierarchical multiple regression indicated that BAL did not predict DRS outcomes after controlling for pertinent covariates. An interaction effect between PI-ETOH and ethnicity was observed, such that presence of chronic alcohol use predicted worse functional outcome for Anglo-Caucasians and African Americans, but more favorable outcome for Hispanics. Conclusions Ethnic differences in BALs within our severe TBI sample mirrored ethnic drinking patterns observed in the general population, with Hispanics having the highest BALs. A paradoxical relationship between PI-ETOH and functional outcome was observed for Hispanics. PMID:22955101

  5. Psychosocial stressors and alcohol use, severity, and treatment receipt across human immunodeficiency virus (HIV) status in a nationally representative sample of US residents.

    PubMed

    Williams, Emily C; Joo, Young Sun; Lipira, Lauren; Glass, Joseph E

    2017-01-01

    Human immunodeficiency virus (HIV) is stigmatized and disproportionately impacts vulnerable populations. Thus, people living with HIV (PLWH) may have greater exposure to psychosocial stressors than those without HIV. Exposure to psychosocial stressors may increase alcohol use and serve as barriers to alcohol treatment receipt. The authors evaluate whether psychosocial stressors and alcohol use, symptom severity, and treatment receipt vary across HIV status in a general population sample of US residents and assess whether psychosocial stressors mediate identified associations. Data from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were used to assess associations between HIV status and psychosocial stressors (perceived stress, alcohol-related stigma, and perceived discrimination based on race/ethnicity, sexual orientation, or sex) and alcohol-related outcomes (any use, heavy drinking, symptom severity, and treatment receipt). For each outcome, regression models were fit and iteratively adjusted for sociodemographic characteristics and comorbidities. Indirect effects of HIV on alcohol-related outcomes through stressors were estimated to assess mediation when main effects were significant. Among 34,653 NESARC Wave 2 respondents, 161 were PLWH. PLWH were more likely than those without HIV to experience discrimination and had higher levels of perceived stress than those without HIV (P values <.05), but the 2 groups did not differ regarding alcohol-related stigma. PLWH were less likely to use alcohol and had similar rates of heavy drinking relative to participants without HIV, but alcohol symptom severity and treatment receipt were greater among PLWH. Perceived stress but not discrimination mediated associations. Findings from this first study of variation in psychosocial stressors and alcohol use, severity, and treatment receipt across HIV status further highlight PLWH as a population that is particularly vulnerable to

  6. Alcohol disrupts sleep homeostasis.

    PubMed

    Thakkar, Mahesh M; Sharma, Rishi; Sahota, Pradeep

    2015-06-01

    Alcohol is a potent somnogen and one of the most commonly used "over the counter" sleep aids. In healthy non-alcoholics, acute alcohol decreases sleep latency, consolidates and increases the quality (delta power) and quantity of NREM sleep during the first half of the night. However, sleep is disrupted during the second half. Alcoholics, both during drinking periods and during abstinences, suffer from a multitude of sleep disruptions manifested by profound insomnia, excessive daytime sleepiness, and altered sleep architecture. Furthermore, subjective and objective indicators of sleep disturbances are predictors of relapse. Finally, within the USA, it is estimated that societal costs of alcohol-related sleep disorders exceeds $18 billion. Thus, although alcohol-associated sleep problems have significant economic and clinical consequences, very little is known about how and where alcohol acts to affect sleep. In this review, we have described our attempts to unravel the mechanism of alcohol-induced sleep disruptions. We have conducted a series of experiments using two different species, rats and mice, as animal models. We performed microdialysis, immunohistochemical, pharmacological, sleep deprivation and lesion studies which suggest that the sleep-promoting effects of alcohol may be mediated via alcohol's action on the mediators of sleep homeostasis: adenosine (AD) and the wake-promoting cholinergic neurons of the basal forebrain (BF). Alcohol, via its action on AD uptake, increases extracellular AD resulting in the inhibition of BF wake-promoting neurons. Since binge alcohol consumption is a highly prevalent pattern of alcohol consumption and disrupts sleep, we examined the effects of binge drinking on sleep-wakefulness. Our results suggest that disrupted sleep homeostasis may be the primary cause of sleep disruption observed following binge drinking. Finally, we have also shown that sleep disruptions observed during acute withdrawal, are caused due to impaired

  7. αCaMKII Autophosphorylation Controls the Establishment of Alcohol Drinking Behavior

    PubMed Central

    Easton, Alanna C; Lucchesi, Walter; Lourdusamy, Anbarasu; Lenz, Bernd; Solati, Jalal; Golub, Yulia; Lewczuk, Piotr; Fernandes, Cathy; Desrivieres, Sylvane; Dawirs, Ralph R; Moll, Gunther H; Kornhuber, Johannes; Frank, Josef; Hoffmann, Per; Soyka, Michael; Kiefer, Falk; Schumann, Gunter; Peter Giese, K; Müller, Christian P

    2013-01-01

    The α-Ca2+/calmodulin-dependent protein kinase II (αCaMKII) is a crucial enzyme controlling plasticity in the brain. The autophosphorylation of αCaMKII works as a ‘molecular memory' for a transient calcium activation, thereby accelerating learning. We investigated the role of αCaMKII autophosphorylation in the establishment of alcohol drinking as an addiction-related behavior in mice. We found that alcohol drinking was initially diminished in αCaMKII autophosphorylation-deficient αCaMKIIT286A mice, but could be established at wild-type level after repeated withdrawals. The locomotor activating effects of a low-dose alcohol (2 g/kg) were absent in αCaMKIIT286A mice, whereas the sedating effects of high-dose (3.5 g/kg) were preserved after acute and subchronic administration. The in vivo microdialysis revealed that αCaMKIIT286A mice showed no dopamine (DA) response in the nucleus accumbens to acute or subchronic alcohol administration, but enhanced serotonin (5-HT) responses in the prefrontal cortex. The attenuated DA response in αCaMKIIT286A mice was in line with altered c-Fos activation in the ventral tegmental area after acute and subchronic alcohol administration. In order to compare findings in mice with the human condition, we tested 23 single-nucleotide polymorphisms (SNPs) in the CAMK2A gene for their association with alcohol dependence in a population of 1333 male patients with severe alcohol dependence and 939 controls. We found seven significant associations between CAMK2A SNPs and alcohol dependence, one of which in an autophosphorylation-related area of the gene. Together, our data suggest αCaMKII autophosphorylation as a facilitating mechanism in the establishment of alcohol drinking behavior with changing the DA–5-HT balance as a putative mechanism. PMID:23459588

  8. Severe dysphagia as the presenting symptom of Wernicke-Korsakoff syndrome in a non-alcoholic man.

    PubMed

    Karaiskos, Ilias; Katsarolis, Ioannis; Stefanis, Leonidas

    2008-02-01

    We present the case of a non-alcoholic man, who, following severe malnutrition, presented with dysphagia that necessitated gastrostomy tube placement. The patient subsequently developed encephalopathy, at which point thiamine deficiency was suspected and thiamine supplementation initiated. The encephalopathy and the dysphagia resolved, but the patient was left with a dense amnestic deficit consistent with Korsakoff syndrome. MRI at the time of the encephalopathy revealed lesions consistent with Wernicke-Korsakoff syndrome. This case represents a remarkable example of Wernicke-Korsakoff syndrome that for a prolonged time period had as its sole manifestation severe dysphagia. To our knowledge, there is only one similar case reported in the literature. This case serves to alert neurologists that isolated dysphagia may be the presenting symptom of this classic neurological syndrome even in the absence of alcoholism.

  9. Association of cardiac disease and alcohol use with the development of severe ciguatera.

    PubMed

    Radke, Elizabeth G; Grattan, Lynn M; Morris, John Glenn

    2013-12-01

    Ciguatera is a foodborne illness that causes severe gastrointestinal and neurologic symptoms, but the risk factors for illness are not well established. In St Thomas, US Virgin Islands, we performed a case-control study for ciguatera, enrolling 47 patients primarily through the emergency department and 141 age- and sex-matched controls identified through an island-wide survey. We used conditional logistic regression to assess health-related risk factors for ciguatera, including comorbidities and alcohol and tobacco use. Cases were more likely than controls to report alcohol consumption at least weekly (odds ratio 5.7, 95% confidence interval 2.7-24.8). Cases also more frequently had a history of heart disease (odds ratio 6.3, 95% confidence interval 1.2-32.7). Previous ciguatera episodes, lower levels of education, and frequent fish consumption also were associated with illness. This study provides preliminary evidence that preexisting health status influences an individual's risk of developing severe ciguatera. There may be a benefit to educating high-risk individuals about preventing ciguatera.

  10. Ground-water withdrawals from the Coastal Plain of New Jersey, 1956-1980

    USGS Publications Warehouse

    Vowinkel, E.F.

    1984-01-01

    Withdrawals and site data for wells with a pump capacity of 100 ,000 gallons per day or greater in the Coastal Plain of New Jersey are stored in computer files for 1956-80. The data are aggregated by computer into tables, graphs and maps to show the distribution of ground-water withdrawals. Withdrawals are reported by type of use and aquifer for each county in the Coastal Plain. Public-supply wells withdraw the largest quantity of ground water in the Coastal Plain, followed by industrial and agricultural wells. In 1980 public-supply withdrawals were about 280 million gallons per day; the maximum monthly rate was about 355 million gallons per day in July, and the lowest was about 215 million gallons per day in February. Average industrial withdrawals were about 65 million gallons per day. Ground-water withdrawals used for agriculture vary significantly during the year. In 1980, about 75 percent of the agricultural withdrawals occurred from June through September. Several aquifers are used as sources of water supply in the Coastal Plain. Five regional aquifers are the major sources of water for public-supply, industrial, or agricultural use. In decreasing order of withdrawals in 1980, in million gallons per day, they are: The Potomac-Raritan-Magothy aquifer system, 243; Kirkwood-Cohansey aquifer system, 70; Atlantic City 800-foot sand, 21; Englishtown aquifer, 12; and the Wenonah-Mount Laurel aquifer system, 5. (USGS)

  11. The association between perceived distress tolerance and cannabis use problems, cannabis withdrawal symptoms, and self-efficacy for quitting cannabis: The explanatory role of pain-related affective distress.

    PubMed

    Manning, Kara; Rogers, Andrew H; Bakhshaie, Jafar; Hogan, Julianna B D; Buckner, Julia D; Ditre, Joseph W; Zvolensky, Michael J

    2018-10-01

    Rates of cannabis use and related problems continue to rise, ranking as the third most common substance use disorder in the United States, behind tobacco and alcohol use. Past work suggests that perceived distress tolerance is related to several clinically significant features of cannabis use (e.g., coping-oriented use). However, there has been little exploration of the mechanisms that may underlie relations between perceived distress tolerance and cannabis use problems, withdrawal severity, and self-efficacy for quitting. The current study sought to examine the experience of pain, which frequently co-occurs with cannabis use (Ashrafioun, Bohnert, Jannausch, & Ilgen, 2015), as an underlying factor in the relation between perceived distress tolerance and cannabis related problems among 203 current cannabis-using adults (29.2% female, M = 37.7 years, SD = 10.2, 63% African American). Results indicated that perceived distress tolerance via pain related affective distress significantly predicted the severity of cannabis use problems (Pm = 0.60), degree of cannabis withdrawal (Pm = 0.39), and lower self-efficacy for quitting cannabis (Pm = 0.36). Future work may usefully explore the role of pain-related affective distress as a mechanistic factor in the context of perceived distress tolerance-cannabis relations. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Dopamine agonist withdrawal syndrome: implications for patient care.

    PubMed

    Nirenberg, Melissa J

    2013-08-01

    Dopamine agonists are effective treatments for a variety of indications, including Parkinson's disease and restless legs syndrome, but may have serious side effects, such as orthostatic hypotension, hallucinations, and impulse control disorders (including pathological gambling, compulsive eating, compulsive shopping/buying, and hypersexuality). The most effective way to alleviate these side effects is to taper or discontinue dopamine agonist therapy. A subset of patients who taper a dopamine agonist, however, develop dopamine agonist withdrawal syndrome (DAWS), which has been defined as a severe, stereotyped cluster of physical and psychological symptoms that correlate with dopamine agonist withdrawal in a dose-dependent manner, cause clinically significant distress or social/occupational dysfunction, are refractory to levodopa and other dopaminergic medications, and cannot be accounted for by other clinical factors. The symptoms of DAWS include anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal ideation, fatigue, orthostatic hypotension, nausea, vomiting, diaphoresis, generalized pain, and drug cravings. The severity and prognosis of DAWS is highly variable. While some patients have transient symptoms and make a full recovery, others have a protracted withdrawal syndrome lasting for months to years, and therefore may be unwilling or unable to discontinue DA therapy. Impulse control disorders appear to be a major risk factor for DAWS, and are present in virtually all affected patients. Thus, patients who are unable to discontinue dopamine agonist therapy may experience chronic impulse control disorders. At the current time, there are no known effective treatments for DAWS. For this reason, providers are urged to use dopamine agonists judiciously, warn patients about the risks of DAWS prior to the initiation of dopamine agonist therapy, and follow patients closely for withdrawal symptoms during dopamine agonist taper.

  13. Nabiximols as an agonist replacement therapy during cannabis withdrawal: a randomized clinical trial.

    PubMed

    Allsop, David J; Copeland, Jan; Lintzeris, Nicholas; Dunlop, Adrian J; Montebello, Mark; Sadler, Craig; Rivas, Gonzalo R; Holland, Rohan M; Muhleisen, Peter; Norberg, Melissa M; Booth, Jessica; McGregor, Iain S

    2014-03-01

    There are no medications approved for treating cannabis dependence or withdrawal. The cannabis extract nabiximols (Sativex), developed as a multiple sclerosis treatment, offers a potential agonist medication for cannabis withdrawal. To evaluate the safety and efficacy of nabiximols in treating cannabis withdrawal. A 2-site, double-blind randomized clinical inpatient trial with a 28-day follow-up was conducted in New South Wales, Australia. Participants included 51 DSM-IV-TR cannabis-dependent treatment seekers. A 6-day regimen of nabiximols (maximum daily dose, 86.4 mg of Δ9-tetrahydrocannabinol and 80 mg of cannabidiol) or placebo with standardized psychosocial interventions during a 9-day admission. Severity of cannabis withdrawal and cravings (Cannabis Withdrawal Scale), retention in withdrawal treatment, and adverse events. Secondary outcomes include postwithdrawal cannabis use, health outcomes, and psychosocial outcomes. Nabiximols treatment significantly reduced the overall severity of cannabis withdrawal relative to placebo (F8,377.97 = 2.39; P = .01), including effects on withdrawal-related irritability, depression, and cannabis cravings. Nabiximols had a more limited, but still positive, therapeutic benefit on sleep disturbance, anxiety, appetite loss, physical symptoms, and restlessness. Nabiximols patients remained in treatment longer during medication use (unadjusted hazard ratio, 3.66 [95% CI, 1.18-11.37]; P = .02), with 2.84 the number needed to treat to achieve successful retention in treatment. Participants could not reliably differentiate between nabiximols and placebo treatment (χ21 = 0.79; P = .67), and those receiving nabiximols did not report greater intoxication (F1,6 = 0.22; P = .97). The number (F1,50 = 0.3; P = .59) and severity (F1,50 = 2.69; P = .10) of adverse events did not differ significantly between groups. Both groups showed reduced cannabis use at follow-up, with no advantage of

  14. Alcohol and Alzheimer's Disease-Does Alcohol Dependence Contribute to Beta-Amyloid Deposition, Neuroinflammation and Neurodegeneration in Alzheimer's Disease?

    PubMed

    Venkataraman, Ashwin; Kalk, Nicola; Sewell, Gavin; Ritchie, Craig W; Lingford-Hughes, Anne

    2017-03-09

    To investigate the underlying neurobiology between alcohol use, misuse and dependence and cognitive impairment, particularly Alzheimer's disease (AD). Review of the literature using searches of Medline, Pubmed, EMBASE, PsycInfo, and meeting abstracts and presentations. The role of alcohol as a risk factor and contributor for cognitive decline associated with AD has received little attention. This is despite the high prevalence of alcohol use, the potential reversibility of a degree of cognitive impairment and the global burden of AD. Until now the focus has largely been on the toxic effects of alcohol, neuronal loss and the role of thiamine. We propose alcohol adds to the cognitive burden seen in dementia through additional mechanisms to neurodegenerative processes or may contribute at various mechanistic points in the genesis and sustenance of AD pathology via neuroinflammation. We describe the common underlying neurobiology in alcohol and AD, and examine ways alcohol likely contributes to neuroinflammation directly via stimulation of Toll-like receptors and indirectly from small bowel changes, hepatic changes, withdrawal and traumatic brain injury to the pathogenesis of AD. Alcohol use, misuse and dependence cause cognitive impairment. We propose alcohol adds to the cognitive burden seen in dementia through additional mechanisms to neurodegenerative processes or may contribute at various mechanistic points in the genesis and sustenance of AD pathology via neuroinflammation. © The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  15. Visualization of groundwater withdrawals

    USGS Publications Warehouse

    Winston, Richard B.; Goode, Daniel J.

    2017-12-21

    Generating an informative display of groundwater withdrawals can sometimes be difficult because the symbols for closely spaced wells can overlap. An alternative method for displaying groundwater withdrawals is to generate a “footprint” of the withdrawals. WellFootprint version 1.0 implements the Footprint algorithm with two optional variations that can speed up the footprint calculation. ModelMuse has been modified in order to generate the input for WellFootprint and to read and graphically display the output from WellFootprint.

  16. Withdrawal When You’re Pregnant

    Cancer.gov

    The nicotine in cigarettes is addictive. That’s why many smokers who decide to quit go through some degree of withdrawal. Quitting smoking while you’re pregnant won’t change withdrawal symptoms. You may still be uncomfortable or feel not quite like yourself. But withdrawal from cigarettes will not harm your baby.

  17. Identification and validation of midbrain Kcnq4 regulation of heavy alcohol consumption in rodents.

    PubMed

    McGuier, Natalie S; Rinker, Jennifer A; Cannady, Reginald; Fulmer, Diana B; Jones, Sara R; Hoffman, Michaela; Mulholland, Patrick J

    2018-05-24

    Currently available pharmacotherapies for treating alcohol use disorder (AUD) suffer from deleterious side effects and are not efficacious in diverse populations. Clinical and preclinical studies provide evidence that the Kcnq family of genes that encode K V 7 channels influence alcohol intake and dependence. K V 7 channels are a class of slowly activating voltage-dependent K + channels that regulate neuronal excitability. Studies indicate that the K V 7 channel positive modulator retigabine can decrease dopaminergic neuron firing, alter dopamine (DA) release, and reduce alcohol intake in heavy drinking rodents. Given the critical nature of ventral tegmental area (VTA) DA to the addiction process and predominant expression of Kcnq4 in DA neurons, we investigated the role of midbrain Kcnq genes and K V 7 channels in the VTA of genetically diverse mice and long-term heavy drinking rats, respectively. Integrative bioinformatics analysis identified negative correlations between midbrain Kcnq4 expression and alcohol intake and seeking behaviors. Kcnq4 expression levels were also correlated with dopaminergic-related phenotypes in BXD strains, and Kcnq4 was present in support intervals for alcohol sensitivity and alcohol withdrawal severity QTLs in rodents. Pharmacological validation studies revealed that VTA K V 7 channels regulate excessive alcohol intake in rats with a high-drinking phenotype. Administration of a novel and selective K V 7.2/4 channel positive modulator also reduced alcohol drinking in rats. Together, these findings indicate that midbrain Kcnq4 expression regulates alcohol-related behaviors in genetically diverse mice and provide evidence that K V 7.4 channels are a critical mediator of excessive alcohol drinking. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Youth social withdrawal behavior (hikikomori): A systematic review of qualitative and quantitative studies.

    PubMed

    Li, Tim M H; Wong, Paul W C

    2015-07-01

    Acute and/or severe social withdrawal behavior among youth was seen as a culture-bound psychiatric syndrome in Japan, but more youth social withdrawal cases in different countries have been discovered recently. However, due to the lack of a formal definition and diagnostic tool for youth social withdrawal, cross-cultural observational and intervention studies are limited. We aimed to consolidate existing knowledge in order to understand youth social withdrawal from diverse perspectives and suggest different interventions for different trajectories of youth social withdrawal. This review examined the current available scientific information on youth social withdrawal in the academic databases: ProQuest, ScienceDirect, Web of Science and PubMed. We included quantitative and qualitative studies of socially withdrawn youths published in English and academic peer-reviewed journals. We synthesized the information into the following categories: (1) definitions of youth social withdrawal, (2) developmental theories, (3) factors associated with youth social withdrawal and (4) interventions for socially withdrawn youths. Accordingly, there are diverse and controversial definitions for youth social withdrawal. Studies of youth social withdrawal are based on models that lead to quite different conclusions. Researchers with an attachment perspective view youth social withdrawal as a negative phenomenon, whereas those who adopt Erikson's developmental theory view it more positively as a process of seeking self-knowledge. Different interventions for socially withdrawn youths have been developed, mainly in Japan, but evidence-based practice is almost non-existent. We propose a theoretical framework that views youth social withdrawal as resulting from the interplay between psychological, social and behavioral factors. Future validation of the framework will help drive forward advances in theory and interventions for youth social withdrawal as an emerging issue in developed

  19. Do managed alcohol programs change patterns of alcohol consumption and reduce related harm? A pilot study.

    PubMed

    Vallance, Kate; Stockwell, Tim; Pauly, Bernie; Chow, Clifton; Gray, Erin; Krysowaty, Bonnie; Perkin, Kathleen; Zhao, Jinhui

    2016-05-09

    Managed alcohol programs (MAPs) are a harm reduction strategy for people with severe alcohol dependence and unstable housing. MAPs provide controlled access to alcohol usually alongside accommodation, meals, and other supports. Patterns of alcohol consumption and related harms among MAP participants and controls from a homeless shelter in Thunder Bay, Ontario, were investigated in 2013. Structured interviews were conducted with 18 MAP and 20 control participants assessed as alcohol dependent with most using non-beverage alcohol (NBA). Qualitative interviews were conducted with seven participants and four MAP staff concerning perceptions and experiences of the program. Program alcohol consumption records were obtained for MAP participants, and records of police contacts and use of health services were obtained for participants and controls. Some participants' liver function test (LFT) results were available for before and after MAP entry. Compared with periods off the MAP, MAP participants had 41 % fewer police contacts, 33 % fewer police contacts leading to custody time (x (2) = 43.84, P < 0.001), 87 % fewer detox admissions (t = -1.68, P = 0.06), and 32 % fewer hospital admissions (t = -2.08, P = 0.03). MAP and control participants shared similar characteristics, indicating the groups were broadly comparable. There were reductions in nearly all available LFT scores after MAP entry. Compared with controls, MAP participants had 43 % fewer police contacts, significantly fewer police contacts (-38 %) that resulted in custody time (x (2) = 66.10, P < 0.001), 70 % fewer detox admissions (t = -2.19, P = 0.02), and 47 % fewer emergency room presentations. NBA use was significantly less frequent for MAP participants versus controls (t = -2.34, P < 0.05). Marked but non-significant reductions were observed in the number of participants self-reporting alcohol-related harms in the domains of home life, legal issues, and

  20. Alcohol and drug dependence symptom items as brief screeners for substance use disorders: results from the Clinical Trials Network

    PubMed Central

    Wu, Li-Tzy; Blazer, Dan G.; Woody, George E.; Burchett, Bruce; Yang, Chongming; Pan, Jeng-Jong; Ling, Walter

    2011-01-01

    Aim To address an urgent need for screening of substance use problems in medical settings, we examined substance-specific dependence criteria as potential brief screeners for the detection of patients with a substance use disorder (SUD). Methods The sample included 920 opioid-dependent adults who were recruited from outpatient treatment settings at 11 programs in 10 U.S. cities and who completed intake assessments of SUDs for a multisite study of the National Drug Abuse Treatment Clinical Trials Network (CTN003). Data were analyzed by factor analysis, item response theory (IRT), sensitivity, and specificity procedures. Results Across all substances (alcohol, amphetamines, cannabis, cocaine, sedatives), withdrawal was among the least prevalent symptoms, while taking large amounts and inability to cut down were among the most prevalent symptoms. Items closely related to the latent trait of a SUD showed good-to-high values of area under the receiver operating characteristic curve in identifying cases of a SUD; IRT-defined severe and less discriminative items exhibited low sensitivity in identifying cases of a SUD (withdrawal for all substances; time using for alcohol and sedatives; giving up activities for sedatives). Conclusions Study results suggest that withdrawal and time using are much less reliable indicators for a SUD than taking larger amounts than intended and inability to cut down and should be studied further for consideration in developing a simplified tool for screening patients for SUDs in medical settings. These findings have implications for the use of common health indicators in electronic health records systems to improve patient care. PMID:22204775

  1. Subacute encephalopathy with epileptic seizures in alcoholism (SESA): case report.

    PubMed

    Otto, F G; Kozian, R

    2001-10-01

    The case of a 66-year-old patient is reported in view of the rarity of his condition: a case of subacute encephalopathy with seizures in alcoholics (SESA syndrome), described first in 1981 by Niedermeyer, et al. Wernicke-type aphasia, epileptic seizures (generalized tonic-clonic) and PLEDs EEG pattern dominated the neurological picture, in addition to hepatomegaly and rhabdomyolysis. This condition differs from all other known CNS complications in chronic alcoholism and is withdrawal-independent. It is prognostically favorable as far as the syndrome as such is concerned.

  2. Do withdrawal-like symptoms mediate increased marijuana smoking in individuals treated with venlafaxine-XR?

    PubMed

    Kelly, Meredith A; Pavlicova, Martina; Glass, Andrew; Mariani, John J; Bisaga, Adam; Sullivan, Maria A; Nunes, Edward V; Levin, Frances R

    2014-11-01

    Cannabis-dependent participants with depressive disorder are less likely to achieve abstinence with venlafaxine-XR (VEN-XR) treatment. Individuals on VEN-XR reported more severe withdrawal, despite not reducing their smoking behavior. We hypothesized that withdrawal-like symptoms, likely medication side effects, led to continued marijuana smoking in this group. We conducted a secondary analysis using Marijuana Withdrawal Checklist (MWC) scores and urine THC to test whether severity of withdrawal-like symptoms mediates the relationship between VEN-XR treatment and continued marijuana smoking. We included 103 participants (VEN-XR=51, Placebo=52). Marijuana use was dichotomized into smoking (THC>100 ng/ml) and non-smoking (THC ≤ 100 ng/ml) weeks. MWC scores were obtained weekly. We used three models in a regression based mediation analysis. The estimated risk of smoking marijuana was greater for individuals on VEN-XR in weeks 7-9, even when controlling for MWC scores (week 7 Risk Difference (RD)=0.11, p=0.034; week 8 RD=0.20, p=0.014), and higher scores mediated this effect. In weeks 10 and 11, the estimated effect was stronger (week 10 RD=0.03, p=0.380; week 11 RD=0.07, p=0.504), and worse withdrawal-like symptoms more fully accounted for continued marijuana smoking in the VEN-XR group, according to the models. Individuals treated with VEN-XR had more severe withdrawal-like symptoms, which mediated their continued marijuana smoking. Noradrenergic agents, such as VEN-XR, may negatively impact treatment outcomes in cannabis-dependent patients attempting to reduce or stop their use. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Do withdrawal-like symptoms mediate increased marijuana smoking in individuals treated with venlafaxine-XR?

    PubMed Central

    Kelly, Meredith A.; Pavlicova, Martina; Glass, Andrew; Mariani, John J.; Bisaga, Adam; Sullivan, Maria A.; Nunes, Edward V.; Levin, Frances R.

    2014-01-01

    Background and aims Cannabis-dependent participants with depressive disorder are less likely to achieve abstinence with venlafaxine-XR (VEN-XR) treatment. Individuals on VEN-XR reported more severe withdrawal, despite not reducing their smoking behavior. We hypothesized that withdrawal-like symptoms, likely medication side effects, led to continued marijuana smoking in this group. Methods We conducted a secondary analysis using Marijuana Withdrawal Checklist (MWC) scores and urine THC to test whether severity of withdrawal-like symptoms mediates the relationship between VEN-XR treatment and continued marijuana smoking. We included 103 participants (VEN-XR = 51, Placebo = 52). Marijuana use was dichotomized into smoking (THC > 100 ng/ml) and non-smoking (THC ≤ 100 ng/ml) weeks. MWC scores were obtained weekly. We used three models in a regression based mediation analysis. Results The estimated risk of smoking marijuana was greater for individuals on VEN-XR in weeks 7–9, even when controlling for MWC scores (week 7 Risk Difference (RD) = 0.11, p = 0.034; week 8 RD = 0.20, p = 0.014), and higher scores mediated this effect. In weeks 10 and 11, the estimated effect was stronger (week 10 RD = 0.03, p = 0.380; week 11 RD = 0.07, p = 0.504), and worse withdrawal-like symptoms more fully accounted for continued marijuana smoking in the VEN-XR group, according to the models. Conclusions Individuals treated with VEN-XR had more severe withdrawal-like symptoms, which mediated their continued marijuana smoking. Noradrenergic agents, such as VEN-XR, may negatively impact treatment outcomes in cannabis-dependent patients attempting to reduce or stop their use. PMID:25283697

  4. Smoking history, nicotine dependence, and changes in craving and mood during short-term smoking abstinence in alcohol dependent vs. control smokers.

    PubMed

    Heffner, Jaimee L; Mingione, Carolyn; Blom, Thomas J; Anthenelli, Robert M

    2011-03-01

    The goal of this study was to compare lifetime cigarette smoking, severity of nicotine dependence, and subjective effects of short-term tobacco abstinence in abstinent alcohol dependent (AD) and control smokers. AD (n=119) and control (n=55) ever-smokers were compared on tobacco use history and nicotine dependence. Negative affect and craving to smoke were examined in a subsample of currently smoking AD (N=34) and control (N=19) participants during a 6-h period of tobacco abstinence using the Profile of Mood States (POMS) and the Questionnaire on Smoking Urges-Brief (QSU-B). Although AD smokers did not differ from controls on heaviness of smoking, they were more likely to meet lifetime criteria for nicotine dependence. AD smokers also reported more withdrawal symptoms and were more likely to endorse withdrawal-related depressed mood during past smoking reduction or abstinence periods. During short-term abstinence, AD smokers were more likely to report high craving to smoke for negative affect relief within the first 150 min of tobacco abstinence, but did not differ from controls on overall craving to smoke or withdrawal-related negative affect on the POMS. Results support previous findings that AD smokers have a greater prevalence of nicotine dependence and more severe nicotine withdrawal, with a greater propensity toward withdrawal-related depressed mood. These results, along with our novel finding that greater craving to smoke in abstaining smokers with AD is specific to negative affect-related craving, suggest that negative reinforcement may be a particularly salient factor in the maintenance of tobacco use among individuals with AD. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. Trajectories of social withdrawal and cognitive decline in the schizophrenia prodrome.

    PubMed

    Cullen, Kathryn; Guimaraes, Angela; Wozniak, Jeffrey; Anjum, Afshan; Schulz, S Charles; White, Tonya

    2011-01-01

    Schizophrenia is a heterogeneous neurodevelopmental disorder. Patients with high levels of negative symptoms have been identified as a specific subtype, but little is known about how the neurodevelopmental course may differ in this group. This study aimed to characterize developmental trajectories of premorbid social withdrawal and cognitive decline between patients with high versus low levels of negative symptoms in youth with schizophrenia-spectrum disorders. A standardized timeline was used to delineate the emergence of psychosis, social withdrawal, and cognitive decline in 52 subjects aged 8 to 19 with schizophrenia (n=36), schizophreniform (n=6), or schizoaffective disorder (n=10). The sample was divided into subgroups of high- (n=26) versus low- (n=26) negative symptoms, and developmental trajectories of premorbid symptoms were compared between groups. Mean ages for emergence of social withdrawal, cognitive decline, and psychosis were 11.1 years (SD=2.5), 11.9 (SD=4.4) and 13.2 years (SD=1.2), respectively. In the high-negative symptom group, the premorbid developmental trajectory for social withdrawal was more protracted. This group also had more severe cognitive decline at the onset of psychosis, but the premorbid trajectories for cognitive decline did not differ significantly between groups. This work documents a more severe and protracted trajectory of premorbid social withdrawal in patients with high levels of negative symptoms in comparison to those with low-negative symptoms. The findings reported here are supportive of the hypothesis that patients with illness characterized by high levels of negative symptoms may represent a subgroup with distinct neurodevelopmental abnormalities.

  6. Peptidase inhibitors reduce opiate narcotic withdrawal signs, including seizure activity, in the rat.

    PubMed

    Pinsky, C; Dua, A K; LaBella, F S

    1982-07-15

    Narcotic withdrawal was precipitated by administration of naloxone in a low dose at 2 h after the final dose of morphine in a 9-day dependency-inducing schedule. Withdrawal was characterized by leaps, increased nocifensor activity and by cerebral cortical epileptiform activity, the latter not generally reported to be prominent in narcotic withdrawal. Single large doses of morphine did not provoke epileptiform activity at 2 h postinjection but did induce an acute opioid dependency wherein a moderately high dose of naloxone, ineffective in non-dependent rats, provoked upward leaping and electrocortical epileptiform activity. Pretreatment of the 9-day dependent rats with peptidase inhibitors, administered intracerebroventricularly, significantly reduced withdrawal severity including the epileptiform activity. We propose that peptidase inhibitors protect certain species of endogenous opioids and/or other neuropeptides that tend to suppress expression of the narcotic withdrawal syndrome. Furthermore, our findings suggest that epileptiform activity is a nascent form of cerebral activity hitherto largely unnoticed in narcotic withdrawal and that neuropeptides may be involved in certain epileptic states.

  7. Effects of testosterone undecanoate replacement and withdrawal on cardio-metabolic, hormonal and body composition outcomes in severely obese hypogonadal men: a pilot study.

    PubMed

    Francomano, D; Bruzziches, R; Barbaro, G; Lenzi, A; Aversa, A

    2014-04-01

    Modifications of cardiovascular and metabolic parameters during testosterone (T) replacement and withdrawal have never been investigated in severely obese hypogonadal men. Twenty-four severely obese (mean BMI 42; mean age 54.5) hypogonadal men (mean T = 245 ± 52 ng/dL) were enrolled in an observational, parallel-arm, open-label, 54-week study of hypocaloric diet plus physical activity (DPE; n = 12) or DPE plus T injections (DPE + T; n = 12), followed by 24 weeks of DPE alone. Primary endpoints were variations from baseline of cardiovascular (cardiac performance, blood pressure, endothelial function, carotid intima-media thickness, CIMT; epicardial fat thickness, EF) and body composition (fat/lean mass) parameters. Secondary endpoints were variations from baseline of hormonal (T and GH) and metabolic (oral glucose tolerance test, lipids, fibrinogen) parameters. At 54 weeks, DPE + T showed improvements in EF, ejection fraction, diastolic function, CIMT and endothelial function (p < 0.01 vs. controls). Also, hormonal (T, p < 0.0001; GH, p < 0.01), metabolic (HOMA, p < 0.01; microalbuminuria, p < 0.01), lipid (total cholesterol, p < 0.05) and inflammatory (fibrinogen, p < 0.05) parameters improved. After 24 weeks from T withdrawal, all cardiac and hormonal parameters returned to baseline, while fat but not lean mass and blood pressure ameliorations were maintained. An inverse relationship either between EF vs. endothelial function and EF vs. T levels was found (r (2) = -0.46, p < 0.001 and r (2) = -0.56, p < 0.0005, respectively) while direct relationship between T vs. endothelial function occurred (r (2) = 0.43, p < 0.005) in DPE + T. A 33 % dropout rate was reported in DPE without serious adverse events. In middle-aged hypogonadal obese men, 1-year T treatment was safe and improved cardio-metabolic and hormonal parameters. We firstly demonstrated that T withdrawal determines a return back to hypogonadism within 6 months, with loss of cardiovascular and some body

  8. Asymmetric Partner Pronoun Use and Demand-Withdraw Interaction in Couples Coping with Health Problems

    PubMed Central

    Rentscher, Kelly E.; Rohrbaugh, Michael J.; Shoham, Varda; Mehl, Matthias R.

    2014-01-01

    Recent research links first-person plural pronoun use (we-talk) by individual romantic partners to adaptive relationship functioning and individual health outcomes. To examine a possible boundary condition of adaptive we-talk in couples coping with health problems, we correlated asymmetric couple-level we/I-ratios (more we-talk relative to I-talk by the spouse than the patient) with a concurrent pattern of directional demand-withdraw (D-W) interaction in which the spouse demands change while the patient withdraws. Couples in which a partner who abused alcohol (n = 65), smoked cigarettes despite having heart or lung disease (n = 24), or had congestive heart failure (n = 58) discussed a health-related disagreement during a video-recorded interaction task. Transcripts of these conversations provided measures of pronoun use for each partner, and trained observers coded D-W patterns from the recordings. As expected, partner asymmetry in we/I-ratio scores predicted directional demand-withdraw, such that spouses who used more we-talk (relative to I-talk) than patients tended to assume the demand role in concurrent D-W interaction. Asymmetric I-talk rather than we-talk accounted for this association, and asymmetric you-talk contributed independently as well. In contrast to previous studies of we-talk by individual partners, the present results identify dyad-level pronoun patterns that clearly do not mark beneficent processes: asymmetric partner we/I-ratios and you-talk reflect problematic demand-withdraw interaction. PMID:24098961

  9. Impaired decision-making and brain shrinkage in alcoholism.

    PubMed

    Le Berre, A-P; Rauchs, G; La Joie, R; Mézenge, F; Boudehent, C; Vabret, F; Segobin, S; Viader, F; Allain, P; Eustache, F; Pitel, A-L; Beaunieux, H

    2014-03-01

    Alcohol-dependent individuals usually favor instant gratification of alcohol use and ignore its long-term negative consequences, reflecting impaired decision-making. According to the somatic marker hypothesis, decision-making abilities are subtended by an extended brain network. As chronic alcohol consumption is known to be associated with brain shrinkage in this network, the present study investigated relationships between brain shrinkage and decision-making impairments in alcohol-dependent individuals early in abstinence using voxel-based morphometry. Thirty patients performed the Iowa Gambling Task and underwent a magnetic resonance imaging investigation (1.5T). Decision-making performances and brain data were compared with those of age-matched healthy controls. In the alcoholic group, a multiple regression analysis was conducted with two predictors (gray matter [GM] volume and decision-making measure) and two covariates (number of withdrawals and duration of alcoholism). Compared with controls, alcoholics had impaired decision-making and widespread reduced gray matter volume, especially in regions involved in decision-making. The regression analysis revealed links between high GM volume in the ventromedial prefrontal cortex, dorsal anterior cingulate cortex and right hippocampal formation, and high decision-making scores (P<0.001, uncorrected). Decision-making deficits in alcoholism may result from impairment of both emotional and cognitive networks. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  10. Nicotine Withdrawal; Measure Your Symptoms (Quiz)

    MedlinePlus

    ... Free Resources Medications Can Help You Quit Using Nicotine Replacement Therapy Busting NRT Myths Smokefree Phone Apps ... Withdrawal Understanding Withdrawal Quiz: How Strong is Your Nicotine Addiction? Quiz: What Are Your Withdrawal Symptoms? Dealing ...

  11. Withholding and withdrawing of life support from patients with severe head injury.

    PubMed

    O'Callahan, J G; Fink, C; Pitts, L H; Luce, J M

    1995-09-01

    To characterize the withholding or withdrawing of life support from patients with severe head injury. San Francisco General Hospital, a city and county hospital with a Level I trauma center. A standardized questionnaire was used to collect data on demographics and functional outcome of severely head-injured (Glasgow Coma Score of < or = 7) patients admitted to the medical-surgical intensive care unit, and to interview the patients' physician and family members. Forty-seven patients who were admitted to a medical-surgical intensive care unit over a 1-yr period. Twenty-four patients had life support withheld or withdrawn, and 23 patients did not. Physician and family separately assessed patient's probable functional outcome, degree of communication between them, reasons important in recommending or deciding on discontinuation of life support, and the result of action taken. Six months later, the families reviewed the process of their decision, how well physician(s) had communicated, and what might have improved communication. Of 24 patients with life support discontinued, 22 died; two were discharged from the hospital. Twenty-three of the 24 patients had a poor prognosis on admission. Of the 23 patients who were continued on life support for the duration of their hospitalization, ten had a poor (p < .001) prognosis on admission. Prognosis improved for two patients from the first group and five from the latter. Family's assessment of prognosis agreed with physician's assessment in 22 of the 24 patients from whom life support was discontinued (p < .001). Physicians' ability to convey the prognosis appeared to influence families' assessments. Physicians' considerations in recommending limitation of care and families' considerations in making decisions were the same, primarily an inevitably poor prognosis. Neither physician nor families cited cost or availability of care as a deciding factor. Two families disagreed with the recommendation to limit care after initial

  12. Extreme halophilic alcohol dehydrogenase mediated highly efficient syntheses of enantiopure aromatic alcohols.

    PubMed

    Alsafadi, Diya; Alsalman, Safaa; Paradisi, Francesca

    2017-11-07

    Enzymatic synthesis of enantiopure aromatic secondary alcohols (including substituted, hetero-aromatic and bicyclic structures) was carried out using halophilic alcohol dehydrogenase ADH2 from Haloferax volcanii (HvADH2). This enzyme showed an unprecedented substrate scope and absolute enatioselectivity. The cofactor NADPH was used catalytically and regenerated in situ by the biocatalyst, in the presence of 5% ethanol. The efficiency of HvADH2 for the conversion of aromatic ketones was markedly influenced by the steric and electronic factors as well as the solubility of ketones in the reaction medium. Furthermore, carbonyl stretching band frequencies ν (C[double bond, length as m-dash]O) have been measured for different ketones to understand the effect of electron withdrawing or donating properties of the ketone substituents on the reaction rate catalyzed by HvADH2. Good correlation was observed between ν (C[double bond, length as m-dash]O) of methyl aryl-ketones and the reaction rate catalyzed by HvADH2. The enzyme catalyzed the reductions of ketone substrates on the preparative scale, demonstrating that HvADH2 would be a valuable biocatalyst for the preparation of chiral aromatic alcohols of pharmaceutical interest.

  13. Perception of sweet taste is important for voluntary alcohol consumption in mice.

    PubMed

    Blednov, Y A; Walker, D; Martinez, M; Levine, M; Damak, S; Margolskee, R F

    2008-02-01

    To directly evaluate the association between taste perception and alcohol intake, we used three different mutant mice, each lacking a gene expressed in taste buds and critical to taste transduction: alpha-gustducin (Gnat3), Tas1r3 or Trpm5. Null mutant mice lacking any of these three genes showed lower preference score for alcohol and consumed less alcohol in a two-bottle choice test, as compared with wild-type littermates. These null mice also showed lower preference score for saccharin solutions than did wild-type littermates. In contrast, avoidance of quinine solutions was less in Gnat3 or Trpm5 knockout mice than in wild-type mice, whereas Tas1r3 null mice were not different from wild type in their response to quinine solutions. There were no differences in null vs. wild-type mice in their consumption of sodium chloride solutions. To determine the cause for reduction of ethanol intake, we studied other ethanol-induced behaviors known to be related to alcohol consumption. There were no differences between null and wild-type mice in ethanol-induced loss of righting reflex, severity of acute ethanol withdrawal or conditioned place preference for ethanol. Weaker conditioned taste aversion (CTA) to alcohol in null mice may have been caused by weaker rewarding value of the conditioned stimulus (saccharin). When saccharin was replaced by sodium chloride, no differences in CTA to alcohol between knockout and wild-type mice were seen. Thus, deletion of any one of three different genes involved in detection of sweet taste leads to a substantial reduction of alcohol intake without any changes in pharmacological actions of ethanol.

  14. PERCEPTION OF SWEET TASTE IS IMPORTANT FOR VOLUNTARY ALCOHOL CONSUMPTION IN MICE

    PubMed Central

    Blednov, Y.A.; Walker, D.; Martinez, M.; Levine, M.; Damak, S.; Margolskee, R.F.

    2012-01-01

    To directly evaluate the association between taste perception and alcohol intake, we used three different mutant mice, each lacking a gene expressed in taste buds and critical to taste transduction: α-gustducin (Gnat3), Tas1r3 or Trpm5. Null mutant mice lacking any of these three genes showed lower preference score for alcohol and consumed less alcohol in a two-bottle choice test, as compared with wild-type littermates. These null mice also showed lower preference score for saccharin solutions than did wild-type littermates. In contrast, avoidance of quinine solutions was less in Gnat3 or Trpm5 knockout mice than in wild type mice, whereas Tas1r3 null mice were not different from wild-type in their response to quinine solutions. There were no differences in null vs. wild-type mice in their consumption of sodium chloride solutions. To determine the cause for reduction of ethanol intake, we studied other ethanol-induced behaviors known to be related to alcohol consumption. There were no differences between null and wild-type mice in ethanol-induced loss of righting reflex, severity of acute ethanol withdrawal or conditioned place preference for ethanol. Weaker conditioned taste aversion to alcohol in null mice may have been caused by weaker rewarding value of the conditioned stimulus (saccharin). When saccharin was replaced by sodium chloride, no differences in conditioned taste aversion to alcohol between knockout and wild-type mice were seen. Thus, deletion of any one of three different genes involved in detection of sweet taste leads to a substantial reduction of alcohol intake without any changes in pharmacological actions of ethanol. PMID:17376151

  15. Qualitative analysis of high-risk drug and alcohol use situations among severely mentally ill substance abusers.

    PubMed

    Bradizza, Clara M; Stasiewicz, Paul R

    2003-01-01

    Situational factors have been found to influence relapse to alcohol and drug use in general samples of substance abusers. However, little research exists examining the influence of interpersonal and intrapersonal determinants in samples of individuals dually diagnosed with a severe mental illness (SMI) and a substance use disorder (SUD). This study assessed high-risk alcohol and drug use situations in dually diagnosed individuals using focus group methodology. Qualitative data analysis yielded 10 themes that encompassed 33 high-risk situations: Psychological symptoms, positive and negative affect, reminders of substance use, being around people who use drugs and alcohol, interpersonal conflict, offers of drugs or alcohol, experiencing loss, receiving money, loss of appetite, and being abstinent. These results suggest that individuals with an SMI and SUD experience a number of unique high-risk situations that differ from those reported by non-SMI substance abusers. This study provides the basis for future quantitative studies assessing the prevalence of these situations in representative samples of SMI alcohol and drug abusers. This information allows for the development of relapse assessment instruments and treatment strategies appropriate for this population. Copyright 2002 Elsevier Science Ltd.

  16. Alcohol dependence and opiate dependence: lack of relationship in mice.

    PubMed

    Goldstein, A; Judson, B A

    1971-04-16

    According to a recently proposed hypothesis, physical dependence upon alcohol is due to the formation of an endogenous opiate. We tested the hypothesis by determining whether or not ethanol-dependent mice would show typical opiate-dependent behavior (withdrawal jumping syndrome) when challenged with the opiate antagonist naloxone. Our results do not support the hypothesis.

  17. Alcohol Use Severity and Depressive Symptoms among Late Adolescent Hispanics: Testing Associations of Acculturation and Enculturation in a Bicultural Transaction Model

    PubMed Central

    Cano, Miguel Ángel; de Dios, Marcel A.; Castro, Yessenia; Vaughan, Ellen L.; Castillo, Linda G.; Lorenzo-Blanco, Elma I.; Piña-Watson, Brandy; Cardoso, Jodi Berger; Ojeda, Lizette; Cruz, Rick A.; Correa-Fernandez, Virmarie; Ibañez, Gladys; Auf, Rehab; Molleda, Lourdes M.

    2015-01-01

    Research has indicated that Hispanics have high rates of heavy drinking and depressive symptoms during late adolescence. The purpose of this study was to test a bicultural transaction model composed of two enthnocultural orientations (acculturation and enculturation); and stressful cultural transactions with both the U.S. culture (perceived ethnic discrimination) and Hispanic culture (perceived intragroup marginalization) to predict alcohol use severity and depressive symptoms among a sample of 129 (men = 39, women = 90) late adolescent Hispanics (ages 18 to 21) enrolled in college. Results from a path analysis indicated that the model accounted for 18.2% of the variance in alcohol use severity and 24.3% of the variance in depressive symptoms. None of the acculturation or enculturation domains had statistically significant direct effects with alcohol use severity or depressive symptoms. However, higher reports of ethnic discrimination were associated with higher reports of alcohol use severity and depressive symptoms. Similarly, higher reports of intragroup marginalization were associated with higher depressive symptoms. Further, both ethnic discrimination and intragroup marginalization functioned as mediators of multiple domains of acculturation and enculturation. These findings highlight the need to consider the indirect effects of enthnocultural orientations in relation to health-related outcomes. PMID:26092776

  18. Modeling the Diagnostic Criteria for Alcohol Dependence with Genetic Animal Models

    PubMed Central

    Kendler, Kenneth S.; Hitzemann, Robert J.

    2012-01-01

    A diagnosis of alcohol dependence (AD) using the DSM-IV-R is categorical, based on an individual’s manifestation of three or more symptoms from a list of seven. AD risk can be traced to both genetic and environmental sources. Most genetic studies of AD risk implicitly assume that an AD diagnosis represents a single underlying genetic factor. We recently found that the criteria for an AD diagnosis represent three somewhat distinct genetic paths to individual risk. Specifically, heavy use and tolerance versus withdrawal and continued use despite problems reflected separate genetic factors. However, some data suggest that genetic risk for AD is adequately described with a single underlying genetic risk factor. Rodent animal models for alcohol-related phenotypes typically target discrete aspects of the complex human AD diagnosis. Here, we review the literature derived from genetic animal models in an attempt to determine whether they support a single-factor or multiple-factor genetic structure. We conclude that there is modest support in the animal literature that alcohol tolerance and withdrawal reflect distinct genetic risk factors, in agreement with our human data. We suggest areas where more research could clarify this attempt to align the rodent and human data. PMID:21910077

  19. Sedatives for opiate withdrawal in newborn infants.

    PubMed

    Osborn, David A; Jeffery, Heather E; Cole, Michael J

    2010-10-06

    reported addition of phenobarbitone significantly reduced the proportion of time infants had a high abstinence severity score, duration of hospitalisation and maximal daily dose of opiate. Infants with NAS due to opiate withdrawal should receive initial treatment with an opiate. Where a sedative is used, phenobarbitone should be used in preference to diazepam. In infants treated with an opiate, the addition of phenobarbitone or clonidine may reduce withdrawal severity. Further studies are needed to determine the role of sedatives in infants with NAS due to opiate withdrawal and the safety and efficacy of adding phenobarbitone or clonidine in infants treated with an opiate for NAS.

  20. THE PREVALENCE OF CANNABIS WITHDRAWAL AND ITS INFLUENCE ON ADOLESCENTS’ TREATMENT RESPONSE AND OUTCOMES: A 12-MONTH PROSPECTIVE INVESTIGATION

    PubMed Central

    Greene, M. Claire; Kelly, John F.

    2014-01-01

    Background Withdrawal, a diagnostic indicator of cannabis use disorder, is often minimized or ignored as a consequence of cannabis use, particularly among adolescents. This study aims to characterize cannabis withdrawal among adolescents in outpatient treatment for substance use disorder and evaluate the clinical significance of withdrawal as a predictor of substance-related outcomes. Methods Adolescent outpatients (N=127) reporting cannabis as their drug of choice (n=90) were stratified by presence of withdrawal and compared on demographic and clinical variables at treatment intake. Hierarchical linear models compared the effect of withdrawal on percent days abstinent (PDA) and related outcomes over a 1-year follow-up period. Results Adolescents reporting withdrawal (40%) were more likely to meet criteria for cannabis dependence, have higher levels of substance use severity, report more substance-related consequences, and have a mood disorder. Withdrawal was not associated with PDA over the follow-up period; however, this relationship was moderated by problem recognition such that adolescents reporting withdrawal and a drug problem improved at a greater rate with respect to PDA than those that didn’t recognize a problem with drugs and didn’t report withdrawal. Discussion Withdrawal is common among adolescent outpatients and is associated with a more clinically severe profile. In this sample, all adolescents reporting withdrawal met criteria for cannabis dependence, suggesting that withdrawal is a highly specific indicator of cannabis use disorder. While withdrawal doesn’t appear to be independently associated with substance use outcomes post-treatment, moderating factors such as drug problem recognition should be taken into account when formulating treatment and continuing care plans. PMID:25100311

  1. The effect of alcohol use on human adolescent brain structures and systems.

    PubMed

    Squeglia, Lindsay M; Jacobus, Joanna; Tapert, Susan F

    2014-01-01

    This article reviews the neurocognitive and neuroimaging literature regarding the effect of alcohol use on human adolescent brain structure and function. Adolescents who engage in heavy alcohol use, even at subdiagnostic levels, show differences in brain structure, function, and behavior when compared with non-drinking controls. Preliminary longitudinal studies have helped disentangle premorbid factors from consequences associated with drinking. Neural abnormalities and cognitive disadvantages both appear to predate drinking, particularly in youth who have a family history of alcoholism, and are directly related to the neurotoxic effect of alcohol use. Binge drinking and withdrawal and hangover symptoms have been associated with the greatest neural abnormalities during adolescence, particularly in frontal, parietal, and temporal regions. © 2014 Elsevier B.V. All rights reserved.

  2. Anticonvulsants for alcohol dependence.

    PubMed

    Pani, Pier Paolo; Trogu, Emanuela; Pacini, Matteo; Maremmani, Icro

    2014-02-13

    anticonvulsants reduced drinks/drinking days (11 studies, 1126 participants, mean difference (MD) -1.49, 95% Cl -2.32 to -0.65) and heavy drinking (12 studies, 1129 participants, standardised mean difference (SMD) -0.35, 95% Cl -0.51 to -0.19). Moreover, withdrawal for medical reasons (12 studies, 1410 participants, RR 1.22, 95% Cl 0.58 to 2.56, moderate-quality evidence) showed no evidence of difference, but for specific adverse effects (nine studies, 1164 participants), two of 18 adverse event outcomes favoured placebo. The direction of results was confirmed by subgroup analyses for topiramate and partially for gabapentin and valproate.Anticonvulsants versus naltrexone: No evidence of difference was shown in dropout rates (five studies, 528 participants, RR 0.74, 95% CI 0.52 to 1.06), severe relapse rates (four studies, 427 participants, RR 0.69, 95% Cl 0.44 to 1.07) and continuous abstinence rates (five studies, 528 participants, RR 1.21, 95% Cl 0.99 to 1.49); anticonvulsants were associated with fewer heavy drinking days (three studies, 308 participants, MD -5.21, 95% Cl -8.58 to -1.83), more days to severe relapse (three studies, 244 participants, MD 11.88, 95% Cl 3.29 to 20.46) and lower withdrawal for medical reasons (three studies, 245 participants, RR 0.13, 95% Cl 0.03 to 0.58). At the current stage of research, randomised evidence supporting the clinical use of anticonvulsants to treat alcohol dependence is insufficient. Results are conditioned by heterogeneity and by the low number and quality of studies comparing anticonvulsants with other medications. The uncertainty associated with these results leaves to clinicians the need to balance possible benefits/risks of treatment with anticonvulsants versus other medications as supported by evidence of efficacy.

  3. An exploration of alcohol use severity and route of drug administration among persons that use heroin and cocaine.

    PubMed

    Scherer, Michael; Harrell, Paul T; Trenz, Rebecca C; Canham, Sarah; Latimer, William W

    2016-01-01

    Alcohol use is prevalent among populations of persons that use illicit drugs. Problematic alcohol use among persons that use heroin and cocaine has been associated with poor treatment adherence, abstinence maintenance, and mental health concerns. Fully exploring how alcohol use severity interacts with route of administration (ROA) may be of notable importance in development of treatment protocols for persons that use heroin and cocaine. Data from a neurological and sociobehavioral assessment of risk factors among injection and noninjection drug users known as the NEURO-HIV Epidemiologic Study was used in the analyses. Participants (N = 551) included those who reported their level of past-30-day alcohol use and past-6-month heroin and cocaine use. Multiple logistic regression analyses found that both problematic and moderate alcohol users were significantly less likely than abstainers to report injecting heroin and cocaine. Both problematic and moderate alcohol users were significantly more likely than abstainers to snort substances. Alcohol use may play a role in promoting or impeding the use of substances through certain ROAs. Treatment protocols that transition persons that use injection heroin and cocaine to noninjection use of these substances may be used in conjunction with treatments that reduce alcohol consumption as a means to reduce noninjection drug use.

  4. Evaluating Distal and Proximal Explanations for Withdrawal: A Rejoinder to Varnum and Kwon's "The Ecology of Withdrawal".

    PubMed

    Norasakkunkit, Vinai; Uchida, Yukiko; Takemura, Kosuke

    2017-01-01

    In their 2016 commentary on our theorizing about how youth withdrawal from economic and social participation in Japanese society (i.e., NEET and Hikikomori phenomena) stems from generational inequality of economic opportunities, Varnum and Kwon correctly point out that our explanation for withdrawal is yet untested. They then offered an alternative, evolutionary psychological explanation for withdrawal in which they claim that in resource-rich ecologies like Japan, the option to withdraw from participating in society is a possible life strategy, a strategy that would be much more costly in resource-poor ecologies. While we agree with this premise, we argue that this distal explanatory framework, at least in its current form, has limits in reconciling some of the more recent cross-cultural observations, as well as well-established sociological claims about the causes of withdrawal. Thus we argue that much work remains in refining and expanding the explanatory power of more distal explanations on the issue of withdrawal. Until then, the more proximal and culture-specific explanations are probably the useful and meaningful explanations for the withdrawal phenomenon.

  5. Estimated freshwater withdrawals in Texas, 1990

    USGS Publications Warehouse

    Lurry, Dee L.

    1994-01-01

    This report presents 1990 freshwater withdrawal estimates for Texas by source and category. Withdrawal source is either ground water or surface water. Withdrawal categories include: self-supplied irrigation, thermoelectric-power generation, water supply, industrial and mining, and other (domestic, commercial, livestock). Withdrawal data are aggregated by county, major aquifer, and principal river basin. Only the four major categories of irrigation, thermoelectric-power generation, water supply, and industrial and mining are illustrated in this report, although all data are tabulated.

  6. Jogging Therapy for Hikikomori Social Withdrawal and Increased Cerebral Hemodynamics: A Case Report.

    PubMed

    Nishida, Masaki; Kikuchi, Senichiro; Fukuda, Kazuhito; Kato, Satoshi

    2016-01-01

    Severe social withdrawal, called hikikomori, has drawn increased public attention. However, an optimal clinical approach and strategy of treatment has not been well established. Here, we report a case of hikikomori for which an exercise intervention using jogging therapy was effective, showing cerebral hemodynamic improvement. The patient was a 20 year old Japanese male who was hospitalized in order to evaluate and treat severe social withdrawal. Although depressive and anxiety symptoms partially subsided with sertraline alone, social withdrawal persisted due to a lack of self confidence. With his consent, we implemented exercise therapy with 30 minutes of jogging three times a week for three months. We did not change the pharmacotherapy, and his social withdrawal remarkably improved with continuous jogging exercise. Using near infrared spectroscopy to evaluate hemodynamic alteration, bilateral temporal hemodynamics considerably increased after the three-month jogging therapy. Regarding exercise therapy for mental illness, numerous studies have reported the effectiveness of exercise therapy for major depression. This case implied, however, that the applicability of exercise therapy is not limited to major depressive disorder. Jogging therapy may contribute to reinforcing self confidence associated with "resilience" in conjunction with neurophysiological modulation of neural networks.

  7. Brief report: Perceptions of social withdrawal during emerging adulthood in Lagos, Nigeria.

    PubMed

    Bowker, Julie C; Ojo, Adesola Adebusola; Bowker, Matthew H

    2016-02-01

    The study of social withdrawal subtypes is no longer limited to Western societies but has extended to non-Western countries, such as China. This study considers, for the first time, social withdrawal subtypes in an African country (Nigeria) by examining emerging adults' (N = 151; 54% female; Mage = 19.92 years, SD = 2.54) perceptions, attitudes, and responses to shy, unsociable, and socially competent behaviors. Results revealed that Nigerian emerging adults perceived significant differences between shy, unsociable, and socially competent behavior in several ways incommensurate with participants of previous studies conducted in North America, Europe, and China. Findings highlight the diversity of social meanings attached to social withdrawal in non-Western societies, and point to the need for additional research on social withdrawal and its perception in Africa. Copyright © 2015 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  8. Levels of Social Sharing and Clinical Implications for Severe Social Withdrawal in Patients with Personality Disorders.

    PubMed

    Colle, Livia; Pellecchia, Giovanni; Moroni, Fabio; Carcione, Antonino; Nicolò, Giuseppe; Semerari, Antonio; Procacci, Michele

    2017-01-01

    Social sharing capacities have attracted attention from a number of fields of social cognition and have been variously defined and analyzed in numerous studies. Social sharing consists in the subjective awareness that aspects of the self's experience are held in common with other individuals. The definition of social sharing must take a variety of elements into consideration: the motivational element, the contents of the social sharing experience, the emotional responses it evokes, the behavioral outcomes, and finally, the circumstances and the skills which enable social sharing. The primary objective of this study is to explore some of the diverse forms of human social sharing and to classify them according to levels of complexity. We identify four different types of social sharing, categorized according to the nature of the content being shared and the complexity of the mindreading skills required. The second objective of this study is to consider possible applications of this graded model of social sharing experience in clinical settings. Specifically, this model may support the development of graded, focused clinical interventions for patients with personality disorders characterized by severe social withdrawal.

  9. Modeling the Severity of Drinking Consequences in First-Year College Women: An Item Response Theory Analysis of the Rutgers Alcohol Problem Index*

    PubMed Central

    Cohn, Amy M.; Hagman, Brett T.; Graff, Fiona S.; Noel, Nora E.

    2011-01-01

    Objective: The present study examined the latent continuum of alcohol-related negative consequences among first-year college women using methods from item response theory and classical test theory. Method: Participants (N = 315) were college women in their freshman year who reported consuming any alcohol in the past 90 days and who completed assessments of alcohol consumption and alcohol-related negative consequences using the Rutgers Alcohol Problem Index. Results: Item response theory analyses showed poor model fit for five items identified in the Rutgers Alcohol Problem Index. Two-parameter item response theory logistic models were applied to the remaining 18 items to examine estimates of item difficulty (i.e., severity) and discrimination parameters. The item difficulty parameters ranged from 0.591 to 2.031, and the discrimination parameters ranged from 0.321 to 2.371. Classical test theory analyses indicated that the omission of the five misfit items did not significantly alter the psychometric properties of the construct. Conclusions: Findings suggest that those consequences that had greater severity and discrimination parameters may be used as screening items to identify female problem drinkers at risk for an alcohol use disorder. PMID:22051212

  10. Cytokine involvement in stress may depend on corticotrophin releasing factor to sensitize ethanol withdrawal anxiety

    PubMed Central

    Knapp, Darin J.; Whitman, Buddy A.; Wills, Tiffany A.; Angel, Robert A.; Overstreet, David H.; Criswell, Hugh E.; Ming, Zhen; Breese, George R.

    2011-01-01

    Stress has been shown to facilitate ethanol withdrawal-induced anxiety. Defining neurobiological mechanisms through which stress has such actions is important given the associated risk of relapse. While CRF has long been implicated in the action of stress, current results show that stress elevates the cytokine TNFα in the rat brain and thereby implicates cytokines in stress effects. In support of this view, prior TNFα microinjection into the central amygdala (CeA) of rats facilitated ethanol withdrawal-induced anxiety—a response that could not be attributed to an increase in plasma corticosterone. To test for a possible interaction between cytokines and CRF, a CRF1-receptor antagonist (SSR125543) administered prior to the repeated administration of TNFα or MCP-1/CCL2 reduced the magnitude of the withdrawal-induced anxiety. This finding provided evidence for cytokine action being dependent upon CRF. Additionally, the sensitizing effect of stress on withdrawal-induced anxiety was reduced by treating the repeated stress exposure prior to ethanol with the MEK inhibitor SL327. Consistent with cytokines having a neuromediator function distinct from a neuroimmune action, TNFα increased firing rate and GABA release from CeA neurons. Thus, an interaction of glial and neuronal function is proposed to contribute to the interaction of stress and chronic ethanol. Interrupting this potential glial-neuronal interaction could provide a novel means by which to alter the development of emotional states induced by stress that predict relapse in the alcoholic. PMID:21377524

  11. Buprenorphine and a CRF1 antagonist block the acquisition of opiate withdrawal-induced conditioned place aversion in rats.

    PubMed

    Stinus, Luis; Cador, Martine; Zorrilla, Eric P; Koob, George F

    2005-01-01

    Conditioned place aversion in rats has face validity as a measure of the aversive stimulus effects of opiate withdrawal that reflects an important motivational component of opiate dependence. The purpose of the present study was to validate conditioned place aversion as sensitive to medications that will alleviate the aversive stimulus effects of opiate withdrawal in humans, and to extend this model to the exploration of the neuropharmacological basis of the motivational effects of opiate withdrawal. Male Sprague-Dawley rats were implanted with two subcutaneous morphine pellets and 5 days later began place conditioning training following subcutaneous administration of a low dose of naloxone. Animals were subjected to three pairings of a low dose of naloxone (15 microg/kg, s.c.) to one arm of a three-chambered place conditioning apparatus. Buprenorphine administered prior to each pairing dose-dependently blocked the place aversion produced by precipitated opiate withdrawal. A corticotropin-releasing factor-1 (CRF1) receptor antagonist (antalarmin) also reversed the place aversion produced by precipitated opiate withdrawal. Antalarmin did not produce a place preference or place aversion by itself in morphine-dependent rats. No effect was observed with pretreatment of the dopamine partial agonist terguride or the selective serotonin reuptake inhibitor fluoxetine. Also, chronic pretreatment with acamprosate (a glutamate receptor modulator used to prevent relapse in alcohol dependence) did not alter naloxone-induced place aversion. Buprenorphine by itself in dependent rats produced a mild place preference at low doses and a mild place aversion at higher doses. These results suggest that buprenorphine blocks the aversive stimulus effects of precipitated opiate withdrawal in rats and provides some validity for the use of place conditioning as a measure that is sensitive to potential opiate-dependence medications. In addition, these results suggest that CRF1 antagonists

  12. [Typology and systematization of residual mental disorders in alcohol dependence].

    PubMed

    Klimenko, T V; Agafonova, S S

    2007-01-01

    The study of 85 patients with alcohol dependence appointed to forensic psychiatric expertise in the Serbsky research center of social and forensic psychiatry revealed the manifestation of polymorphic psychiatric and behavioral disorders (ICD-10 diagnosis F10.7--residual and late-onset psychotic disorders) after stopping the intoxication, withdrawal and post-withdralwal disorders. Taking into account the multifactor etiology of psychiatric disorders which are observed after ending of the direct effect of alcohol, a possibility of including other ICD-10 items to extend their diagnostics and thus provide the more accurate clinical verification of these states, is discussed.

  13. Comparison of intravenous ethanol versus diazepam for alcohol withdrawal prophylaxis in the trauma ICU: results of a randomized trial.

    PubMed

    Weinberg, Jordan A; Magnotti, Louis J; Fischer, Peter E; Edwards, Norma M; Schroeppel, Thomas; Fabian, Timothy C; Croce, Martin A

    2008-01-01

    Although benzodiazepines are the recommended first-line therapy for the prevention of alcohol withdrawal syndrome (AWS), the administration of intravenous ethanol as an alternative prophylactic agent persists in many surgical ICUs. Advocates of this therapy argue that ethanol provides effective prophylaxis against AWS without the excessive sedation observed with benzodiazepine therapy. No study to date, however, has compared the two therapies with regard to their sedative effects. The purpose of this study was to prospectively evaluate the efficacy of intravenous ethanol compared with benzodiazepines for the prevention of AWS with particular emphasis on the sedative effects of each therapy. During a 15-month period, trauma patients admitted to the ICU with a history of chronic daily alcohol consumption greater than or equal to five beverage equivalents per day were prospectively randomized to one of two 4-day prophylactic regimens: intravenous ethanol infusion (EtOH) versus scheduled-dose diazepam (BENZO). Patients were evaluated with the Riker sedation-agitation scale, a 7-point instrument for the subjective assessment of both sedation (1 = unarousable) and agitation (7 = dangerous agitation). According to protocol, regimens were titrated to achieve and maintain a Riker score of 4 (calm and cooperative). Deviation from a score of 4 during the course of treatment was compared between groups. Fifty patients met study criteria and were randomized after obtainment of informed consent (EtOH, n = 26; BENZO, n = 24). Overall, the EtOH group had a significantly greater proportion of patients who deviated from a score of 4 during the course of treatment (p = 0.020). In both groups, the majority of deviation from a score of 4 reflected periods of under-sedation rather than over-sedation. One patient in the EtOH group failed treatment, requiring diazepam and haloperidol for control of AWS symptoms as per protocol, whereas no patient in the BENZO group failed treatment (p

  14. Alcohol use severity and depressive symptoms among late adolescent Hispanics: Testing associations of acculturation and enculturation in a bicultural transaction model.

    PubMed

    Cano, Miguel Ángel; de Dios, Marcel A; Castro, Yessenia; Vaughan, Ellen L; Castillo, Linda G; Lorenzo-Blanco, Elma I; Piña-Watson, Brandy; Berger Cardoso, Jodi; Ojeda, Lizette; Cruz, Rick A; Correa-Fernandez, Virmarie; Ibañez, Gladys; Auf, Rehab; Molleda, Lourdes M

    2015-10-01

    Research has indicated that Hispanics have high rates of heavy drinking and depressive symptoms during late adolescence. The purpose of this study was to test a bicultural transaction model composed of two enthnocultural orientations (acculturation and enculturation); and stressful cultural transactions with both the U.S. culture (perceived ethnic discrimination) and Hispanic culture (perceived intragroup marginalization) to predict alcohol use severity and depressive symptoms among a sample of 129 (men=39, women=90) late adolescent Hispanics (ages 18-21) enrolled in college. Results from a path analysis indicated that the model accounted for 18.2% of the variance in alcohol use severity and 24.3% of the variance in depressive symptoms. None of the acculturation or enculturation domains had statistically significant direct effects with alcohol use severity or depressive symptoms. However, higher reports of ethnic discrimination were associated with higher reports of alcohol use severity and depressive symptoms. Similarly, higher reports of intragroup marginalization were associated with higher depressive symptoms. Further, both ethnic discrimination and intragroup marginalization functioned as mediators of multiple domains of acculturation and enculturation. These findings highlight the need to consider the indirect effects of enthnocultural orientations in relation to health-related outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Combining the α1-Adrenergic Receptor Antagonist, Prazosin, with the β-Adrenergic Receptor Antagonist, Propranolol, Reduces Alcohol Drinking More Effectively Than Either Drug Alone

    PubMed Central

    Rasmussen, Dennis D; Beckwith, Lauren E; Kincaid, Carrie L; Froehlich, Janice C

    2014-01-01

    Background Evidence suggests that activation of the noradrenergic system may contribute to alcohol drinking in animals and humans. Our previous studies demonstrated that blocking α1-adrenergic receptors with the antagonist, prazosin, decreased alcohol drinking in rats under various conditions. Since noradrenergic activation is also regulated by β-adrenergic receptors, we now examine the effects of the β-adrenergic receptor antagonist, propranolol, alone or in combination with prazosin, on alcohol drinking in rats selectively bred for high voluntary alcohol intake and alcohol preference (P line). Methods Two studies were conducted with male P rats. In study one, rats were allowed to become alcohol-dependent during 14 weeks of ad libitum access to food, water and 20% alcohol and the effect of propranolol (5–15 mg/kg, IP) and prazosin (1–2 mg/kg, IP) on alcohol intake during withdrawal were assessed. In study two, the effect of propranolol (5 mg/kg, IP) and prazosin (2 mg/kg, IP) on alcohol intake following prolonged imposed abstinence was assessed. Results Alcohol drinking following propranolol treatment was variable, but the combination of propranolol + prazosin consistently suppressed alcohol drinking during both alcohol withdrawal and following prolonged imposed abstinence, and the combination of these two drugs was more effective than was treatment with either drug alone. Conclusions Treatment with prazosin + propranolol, or a combination of other centrally active α1- and β-adrenergic receptor antagonists, may assist in preventing alcohol relapse in some individuals. PMID:24891220

  16. Brief interventions to reduce harmful alcohol use among military personnel: lessons learned from the civilian experience.

    PubMed

    Fernandez, William G; Hartman, Roger; Olshaker, Jonathan

    2006-06-01

    Unhealthy alcohol use is among the leading causes of morbidity and mortality in the United States. Among military personnel, service members between the ages 18 and 25 had a 27.3% prevalence of heavy drinking in the previous 30 days, compared to 15.3% among civilians in the same age group. In the civilian world, > 100 million patients are treated in U.S. emergency departments (ED) annually; 7.9% of these visits are alcohol related. Alcohol is associated with a broad range of health consequences that may ultimately present in the ED setting: traumatic injuries (e.g., motor vehicle crashes, intentional violence, falls); environmental injuries (e.g., frostbite); cardiovascular problems (e.g., hypertension, dilated cardiomyopathy); gastrointestinal disorders (e.g., hepatitis, pancreatitis, gastrointestinal bleeding); neurological problems (e.g., encephalopathy, alcohol withdrawal, withdrawal seizures), as well as psychological problems (e.g., depression, suicide). Seminal work has been done to create behavioral interventions for at-risk drinkers. These motivational interventions have been found to be successful in encouraging clients to change their risky behaviors. We present such a technique, called the Brief Negotiated Interview as performed in a civilian ED setting, in hopes of adapting it for use in the military context. Military health care providers could easily adapt this technique to help reduce risky levels of alcohol consumption among service members, retirees, or military dependents.

  17. Opiate-induced dopamine release is modulated by severity of alcohol dependence: an [(18)F]fallypride positron emission tomography study.

    PubMed

    Spreckelmeyer, Katja N; Paulzen, Michael; Raptis, Mardjan; Baltus, Thomas; Schaffrath, Sabrina; Van Waesberghe, Julia; Zalewski, Magdalena M; Rösch, Frank; Vernaleken, Ingo; Schäfer, Wolfgang M; Gründer, Gerhard

    2011-10-15

    Preclinical data implicate the reinforcing effects of alcohol to be mediated by interaction between the opioid and dopamine systems of the brain. Specifically, alcohol-induced release of β-endorphins stimulates μ-opioid receptors (MORs), which is believed to cause dopamine release in the brain reward system. Individual differences in opioid or dopamine neurotransmission have been suggested to be responsible for enhanced liability to abuse alcohol. In the present study, a single dose of the MOR agonist remifentanil was administered in detoxified alcohol-dependent patients and healthy control subjects to mimic the β-endorphin-releasing properties of ethanol and to assess the effects of direct MOR stimulation on dopamine release in the mesolimbic reward system. Availability of D(2/3) receptors was assessed before and after single-dose administration of the MOR agonist remifentanil in 11 detoxified alcohol-dependent patients and 11 healthy control subjects with positron emission tomography with the radiotracer [(18)F]fallypride. Severity of dependence as assessed with the Alcohol Use Disorders Identification Test was compared with remifentanil-induced percentage change in [(18)F]fallypride binding (Δ%BP(ND)). The [(18)F]fallypride binding potentials (BP(ND)s) were significantly reduced in the ventral striatum, dorsal putamen, and amygdala after remifentanil application in both patients and control subjects. In the patient group, ventral striatum Δ%BP(ND) was correlated with the Alcohol Use Disorders Identification Test score. The data provide evidence for a MOR-mediated interaction between the opioid and the dopamine system, supporting the assumption that one way by which alcohol unfolds its rewarding effects is via a MOR-(γ-aminobutyric acid)-dopamine pathway. No difference in dopamine release was found between patients and control subjects, but evidence for a patient-specific association between sensitivity to MOR stimulation and severity of alcohol dependence

  18. Homozygosity for rs738409:G in PNPLA3 is associated with increased mortality following an episode of severe alcoholic hepatitis.

    PubMed

    Atkinson, Stephen R; Way, Michael J; McQuillin, Andrew; Morgan, Marsha Y; Thursz, Mark R

    2017-07-01

    Carriage of rs738409:G in PNPLA3 is associated with an increased risk of developing alcohol-related cirrhosis and has a significant negative effect on survival. Short-term mortality in patients with severe alcoholic hepatitis is high; drinking behaviour is a major determinant of outcome in survivors. The aim of this study was to determine whether carriage of rs738409:G has an additional detrimental effect on survival in this patient group. Genotyping was undertaken in 898 cases with severe alcoholic hepatitis, recruited through the UK Steroids or Pentoxifylline for Alcoholic Hepatitis (STOPAH) trial, and 1188 White British/Irish alcohol dependent controls with no liver injury, recruited via University College London. Subsequent drinking behaviour was classified, in cases surviving ≥90days, as abstinent or drinking. The relationship between rs738409 genotype, drinking behaviour and survival was explored. The frequency of rs738409:G was significantly higher in cases than controls (29.5% vs. 18.9%; p=2.15×10 -15 ; odds ratio 1.80 [95% confidence interval (CI) 1.55-2.08]). Case-mortality at days 28, 90 and 450 was 16%, 25% and 41% respectively. There was no association between rs738409:G and 28-day mortality. Mortality in the 90 to 450-day period was higher in survivors who subsequently resumed drinking (hazard ratio [HR] 2.77, 95% CI 1.79-4.29; p<0.0001) and in individuals homozygous for rs738409:G (HR 1.69, 95% CI 1.02-2.81, p=0.04). Homozygosity for rs738409:G in PNPLA3 confers significant additional risk of medium-term mortality in patients with severe alcoholic hepatitis. Rs738409 genotype may be taken into account when considering treatment options for these patients. Individuals misusing alcohol who carry a particular variant of the gene PNPLA3 are more at risk of developing severe alcoholic hepatitis, a condition with a poor chance of survival. The longer-term outcome in people with this condition who survive the initial illness is strongly influenced by

  19. Management of acute overdose or withdrawal state in intrathecal baclofen therapy.

    PubMed

    Watve, S V; Sivan, M; Raza, W A; Jamil, F F

    2012-02-01

    Individuals who are treated with intrathecal Baclofen (ITB) pump delivery system for intractable spasticity can suffer from severe morbidity as a result of acute overdose or withdrawal of ITB, which can also be life threatening. Current literature has a number of single case studies with different approaches to the management in such states. The aim of this article is to consolidate available evidence and develop treatment pathways for acute ITB overdose and withdrawal states. We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library databases using the keywords 'intrathecal', 'baclofen', 'withdrawal', 'overdose' to identify studies (published up to December 2010) that focused on presentation or treatment of acute overdose and withdrawal state in ITB therapy. Only original articles in English involving adult population were included. Initial search revealed 130 articles. After reading the abstract, 13 studies on ITB overdose and 23 studies on ITB withdrawal were deemed suitable for inclusion. All studies were either single-case studies or case series. Acute ITB overdose is managed with immediate cessation of baclofen delivery through the system, reducing the baclofen load by cerebrospinal fluid aspiration and by providing supportive treatment in an intensive care setting. There is no specific antidote for reversing overdose symptoms. Acute ITB withdrawal is managed by restoring the delivery of ITB, providing supportive care in an intensive care setting and using drugs like low dose propofol or benzodiazepines in selected cases. Early involvement of ITB physicians is strongly recommended.

  20. 5-HT1A receptor-dependent modulation of emotional and neurogenic deficits elicited by prolonged consumption of alcohol.

    PubMed

    Belmer, Arnauld; Patkar, Omkar L; Lanoue, Vanessa; Bartlett, Selena E

    2018-02-01

    Repeated episodes of binge-like alcohol consumption produce anxiety, depression and various deleterious effects including alterations in neurogenesis. While the involvement of the serotonin receptor 1 A (5-HT 1A ) in the regulation of anxiety-like behavior and neurogenesis is well documented, its contribution to alcohol withdrawal-induced anxiety and alcohol-induced deficits in neurogenesis is less documented. Using the Drinking-In-the-Dark (DID) paradigm to model chronic long-term (12 weeks) binge-like voluntary alcohol consumption in mice, we show that the selective partial activation of 5-HT 1A receptors by tandospirone (3 mg/kg) prevents alcohol withdrawal-induced anxiety in a battery of behavioral tests (marble burying, elevated-plus-maze, open-field), which is accompanied by a robust decrease in binge-like ethanol intake (1 and 3 mg/kg). Furthermore, using triple immunolabelling of proliferation and neuronal differentiation markers, we show that long-term DID elicits profound deficits in neurogenesis and neuronal fate specification in the dorsal hippocampus that are entirely reversed by a 2-week chronic treatment with the 5-HT 1A partial agonist tandospirone (3 mg/kg/day). Together, our results confirm previous observations that 5-HT 1A receptors play a pivotal role in alcohol drinking behavior and the associated emotional and neurogenic impairments, and suggest that 5-HT 1A partial agonists represent a promising treatment strategy for alcohol abuse.

  1. A Detection Model of College Withdrawal

    ERIC Educational Resources Information Center

    Pleskac, Timothy J.; Keeney, Jessica; Merritt, Stephanie M.; Schmitt, Neal; Oswald, Frederick L.

    2011-01-01

    Many students during their college careers consider withdrawing from their respective college or university. Understanding why some students decide to withdraw yet others persist has implications for both the well being of students as well as for institutes of higher education. The present study develops a model of the decision to withdraw drawing…

  2. Water Quality Research Program. Simultaneous, Multiple-Level Withdrawal from a Density Stratified Reservoir

    DTIC Science & Technology

    1990-11-01

    Furusawa , M . 1969. "Experiments on Selective Withdrawal into a Sink from a Uniformly Stratified Fluid--Phenomenon of Layer Separation and Middle-Layer...E. Howington prepared this report. Assisting in the testing were Messrs. Jack E. Davis; Calvin Buie, Jr.; Douglas M . White; and Paul Ahlrich; and Ms...virtually horizontal. Several researchers such as Hino and Furusawa (1969), Croach (1971), Hino (1980), and Farrant (1982) have studied withdrawal

  3. Behavioral, biological, and chemical perspectives on targeting CRF1 receptor antagonists to treat alcoholism

    PubMed Central

    Zorrilla, Eric P.; Heilig, Markus; de Wit, Harriet; Shaham, Yavin

    2013-01-01

    Background Alcohol use disorders are chronic disabling conditions for which existing pharmacotherapies have only modest efficacy. In the present review, derived from the 2012 Behavior, Biology and Chemistry “Translational Research in Addiction” symposium, we summarize the anti-relapse potential of corticotropin-releasing factor type 1 (CRF1) receptor antagonists to reduce negative emotional symptoms of acute and protracted alcohol withdrawal and stress-induced relapse to alcohol seeking. Methods We review the biology of CRF1 systems, the activity of CRF1 receptor antagonists in animal models of anxiolytic and antidepressant activity, and experimental findings in alcohol addiction models. We also update the clinical trial status of CRF1 receptor antagonists, including pexacerfont (BMS-562086), emicerfont (GW876008), verucerfont (GSK561679), CP316311, SSR125543A, R121919/NBI30775, R317573/19567470/CRA5626, and ONO-2333Ms. Finally, we discuss the potential heterogeneity and pharmacogenomics of CRF1 receptor pharmacotherapy for alcohol dependence. Results The evidence suggests that brain penetrant-CRF1 receptor antagonists have therapeutic potential for alcohol dependence. Lead compounds with clinically desirable pharmacokinetic properties now exist, and longer receptor residence rates (i.e., slow dissociation) may predict greater CRF1 receptor antagonist efficacy. Functional variants in genes that encode CRF system molecules, including polymorphisms in Crhr1 (rs110402, rs1876831, rs242938) and Crhbp genes (rs10055255, rs3811939) may promote alcohol seeking and consumption by altering basal or stress-induced CRF system activation. Conclusions Ongoing clinical trials with pexacerfont and verucerfont in moderately to highly severe dependent anxious alcoholics may yield insight as to the role of CRF1 receptor antagonists in a personalized medicine approach to treat drug or alcohol dependence. PMID:23294766

  4. Alcohol use, alcohol problems, and problem behavior engagement among students at two schools in northern Mexico

    PubMed Central

    Mancha, Brent E.; Rojas, Vanessa C.; Latimer, William W.

    2012-01-01

    This study examined the association between alcohol use problem severity, defined by number of DSM-IV alcohol Abuse and Dependence symptoms and frequency of alcohol use, and problem behavior engagement among Mexican students. A confidential survey was administered to 1229 students in grades 7–12 at two schools in a northern border city in Mexico. Youths were categorized into five groups based on their alcohol use frequency and symptoms of DSM-IV alcohol Abuse and Dependence, specifically: no lifetime alcohol use, lifetime alcohol use but none in the past year, past year alcohol use, one or two alcohol Abuse or Dependence symptoms, and three or more alcohol Abuse or Dependence symptoms. The association between five levels of alcohol use problem severity and three problem behaviors, lifetime marijuana use, lifetime sexual intercourse, and past year arrest/law trouble, was examined using chi-square or Fisher’s exact tests. Several alcohol use problem severity categories were significantly different with respect to rates of lifetime marijuana use, lifetime sexual intercourse, and past year arrest/law trouble. Higher alcohol use problem severity was associated with greater endorsement of problem behaviors. Knowing about variations in adolescent alcohol use and alcohol problems may be instrumental in determining if youths are also engaging in a range of other risk behaviors. Considering varying levels of alcohol use and alcohol problems is important for effective targeted prevention and treatment interventions. PMID:22840814

  5. Alcohol May Not Cause Partner Violence but It Seems to Make It Worse: A Cross National Comparison of the Relationship between Alcohol and Severity of Partner Violence

    ERIC Educational Resources Information Center

    Graham, Kathryn; Bernards, Sharon; Wilsnack, Sharon C.; Gmel, Gerhard

    2011-01-01

    This study assesses whether severity of physical partner aggression is associated with alcohol consumption at the time of the incident, and whether the relationship between drinking and aggression severity is the same for men and women and across different countries. National or large regional general population surveys were conducted in 13…

  6. Effects of a natural community intervention intensifying alcohol law enforcement combined with a restrictive alcohol policy on adolescent alcohol use.

    PubMed

    Schelleman-Offermans, Karen; Knibbe, Ronald A; Kuntsche, Emmanuel; Casswell, Sally

    2012-12-01

    Determining whether intensified inspections on alcohol retailers, combined with a policy withdrawing liquor licenses if retailers are fined twice per annum, is effective in reducing adolescents' odds to initiate weekly drinking and drunkenness. Causal pathways by which the intervention was assumed to work were tested. A longitudinal (2008, 2009, and 2010) quasi-experimental comparison group design including two Dutch communities, one intervention and one comparison, was used. Outcomes were assessed by following a cohort of 1,327 adolescents (aged 13-15 years at baseline). The intervention resulted in increased retail inspections but only seven sanctions and no repeated sanctions in 1 year. The intervention did not reduce adolescents' odds to initiate weekly drinking. Weekly drinking adolescents in the intervention community were at reduced risk to initiate drunkenness. This effect was not mediated by smaller increases in the frequency of adolescents' alcohol purchases or their perceived ease of purchasing alcohol. Intensified enforcement was effective in preventing adolescent drunkenness. No mediating causal pathways were detected. Effectiveness of enforcement could be increased by adopting enforcement methods with a high likelihood of apprehension, increasing social support for restrictive measures, and mobilizing the community to be more outspoken against adolescent (heavy) drinking. Copyright © 2012 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  7. Water withdrawals in Florida, 2012

    USGS Publications Warehouse

    Marella, Richard L.

    2015-09-01

    The largest percentage of freshwater withdrawals was from the South Florida Water Management District (46 percent), followed by the St. Johns River Water Management District (20 percent), Southwest Florida Water Management District (19 percent), Northwest Florida Water Management District (9 percent), and Suwannee River Water Management District (6 percent). The South Florida Water Management District accounted for the largest percentage of freshwater withdrawals for public-supply use (46 percent), commercial-industrial-mining self-supplied use (24 percent), agricultural self-supplied use (59 percent), and recreational-landscape irrigation use (63 percent). The Northwest Florida Water Management District accounted for the largest percentage of freshwater withdrawals for power-generation use (44 percent), and the Southwest Florida Water Management District accounted for the largest percentage of saline-water withdrawals for power-generation use (58 percent).

  8. Nitrendipine decreases benzodiazepine withdrawal seizures but not the development of benzodiazepine tolerance or withdrawal signs.

    PubMed Central

    Dolin, S. J.; Patch, T. L.; Rabbani, M.; Siarey, R. J.; Bowhay, A. R.; Little, H. J.

    1990-01-01

    1. The effects of the calcium channel blocking agent, nitrendipine, were studied on seizures in mice produced during withdrawal from chronic benzodiazepine treatment and on the development of tolerance to benzodiazepines. 2. Nitrendipine produced a dose-dependent decrease in seizure incidence, when seizures were produced by the partial inverse agonist FG7142 during withdrawal from seven days treatment with flurazepam. 3. Nitrendipine did not raise the seizure thresholds in naïve mice to the full inverse agonist methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), or to the gamma-aminobutyric acid (GABA) antagonist, bicuculline. 4. When given concurrently with flurazepam for seven days, nitrendipine did not affect the incidence of seizures during flurazepam withdrawal. 5. When given concurrently with the benzodiazepines, nitrendipine did not prevent the development of tolerance to midazolam general anaesthesia or tolerance to the ataxic actions of flurazepam or midazolam. 6. Chronic treatment with flurazepam for seven days did not affect the Kd or Bmax of [3H]-nimodipine binding in mouse whole brain or cerebral cortex. 7. These results with benzodiazepines are partially in contrast with those for ethanol, where nitrendipine not only decreased ethanol withdrawal seizures when given acutely, but also prevented the development of tolerance and withdrawal signs when given concurrently with ethanol. However, they do confirm the selectivity of nitrendipine for withdrawal-induced seizures. PMID:1963805

  9. Total water withdrawals in Mississippi, 1990

    USGS Publications Warehouse

    Johnson, P.M.

    1994-01-01

    During 1990, the amount of water withdrawn from ground- and surface-water sources in Mississippi was about 3,600 Mgal/d (million gallons per day). Of this amount, 91 percent, or 3,300 Mgal/d, was withdrawn from freshwater sources. Of the total freshwater withdrawals, about 82 percent, or 2,700 Mgal/d, was withdrawn from ground-water sources. Total water withdrawals in Mississippi in 1990 for eight categories of use were as follows: irrigation, 1,900 Mgal/d; thermoelectric power, 700 Mgal/d; aquaculture, 400 Mgal/d; public supply, 320 Mgal/d; industrial and mining, 270 Mgal/d; domestic, 33 Mgal/d; commercial, 16 Mgal/d; and livestock, 16 Mgal/d. Overall, total withdrawals increased by 20 percent from 1985 to 1990, although the total population decreased about 2 percent. During the same period, total freshwater withdrawals increased by about 17 percent. Total saline with- drawals increased by about 60 percent from 1985 due to an increase in salin withdrawals for thermo- electric power generation. Total fresh and saline surface-water withdrawals decreased by about 6 percent from 1985, due to decrease in surface-water withdrawals for irrigation. Fresh ground-water withdrawals in Mississippi increased by about 33 percent, primarily due to an increase in irrigation. Since 1960, total ground- and surface-water with- drawals increased 70 percent for the same period. Irrigation had the greatest increase in with- drawals since 1960, with a 269 percent increase. Public supply had the second greatest, with a 178 percent increase.

  10. Topiramate (Topamax) reduces conditioned abstinence behaviours and handling-induced convulsions (HIC) after chronic administration of alcohol in Swiss-Webster mice.

    PubMed

    Farook, Justin M; Morrell, Dennis J; Lewis, Ben; Littleton, John M; Barron, Susan

    2007-01-01

    Topiramate has emerged as one of the promising drugs for the treatment of alcoholism and alcohol addiction. Recent studies have shown that topiramate reduces harmful drinking and initiates abstinence in humans, but little is known as to why this drug is effective. In the present study, we examined the effects of topiramate in reducing convulsions during alcohol withdrawal using a procedure called the handling-induced convulsion (HIC) test in male Swiss-Webster mice. In addition, we examined the ability of topiramate to reduce alcohol conditioned and anxiety related behaviours during conditioned abstinence using the elevated plus maze (EPM) test. HICs were examined 10 h after the 3rd daily alcohol (2.5 g/kg; 20% w/v)+4 methylpyrazole (4MP) (9 mg/kg) intraperitoneal (i.p.) injection with topiramate (0, 10 or 20 mg/kg ip) administered 30 min before testing. In the EPM, alcohol (1.75 g/kg; 20%, i.p.) or saline was administered daily for 9 days and subjects were immediately placed on the maze. Anxiety related behaviours included the amount of time spent and number of entries in the open or closed arms and grooming bouts, and conditioned behaviours including the stretched-attend posture were examined 24 h after the last day of alcohol injection. Topiramate (10 and 20 mg/kg) significantly reduced HIC scores (P<0.05) compared to the alcohol/saline group. In the EPM, topiramate (20 mg/kg) reduced the stretched-attend postures (P<0.001) compared to the alcohol/saline group. These findings suggest that topiramate reduces HICs during alcohol withdrawal and alcohol-conditioned behaviours during conditioned abstinence in Swiss-Webster mice.

  11. Are Tobacco Dependence and Withdrawal Related Amongst Heavy Smokers? Relevance to Conceptualizations of Dependence

    PubMed Central

    Baker, Timothy B.; Piper, Megan E.; Schlam, Tanya R.; Cook, Jessica W.; Smith, Stevens S.; Loh, Wei-Yin; Bolt, Daniel

    2013-01-01

    Measured tobacco dependence is typically only modestly related to tobacco withdrawal severity amongst regular smokers making a quit attempt. The weak association between dependence and withdrawal is notable because it conflicts with core theories of dependence and because both measures predict cessation outcomes, suggesting they both index a common dependence construct. This study used data from a smoking cessation comparative effectiveness trial (N = 1504) to characterize relations of tobacco dependence with craving and negative affect withdrawal symptoms using multiple dependence measures and analytic methods to detect both additive and interactive effects and to determine whether withdrawal meaningfully mediates the influence of dependence on smoking cessation. We conclude: (1) while univariate analyses suggest dependence and withdrawal measures are only modestly interrelated, more powerful analytic techniques show they are, in fact, meaningfully related and their shared variance is associated with cessation likelihood; (2) there are clear differences between craving and negative affective withdrawal symptoms, with the former more related to smoking heaviness and the latter related to trait measures of negative affect; moreover, craving more strongly mediates dependence effects on cessation; (3) both craving and negative affect withdrawal symptoms are strongly related to a pattern of regular smoking that is sensitive to the passage of time and powerfully affected by smoking cues. These findings support models that accord an important role for associative processes and withdrawal symptoms, especially craving, in drug dependence. The findings also support the use of withdrawal variables as criteria for the evaluation of dependence measures. PMID:22642839

  12. Contribution of early environmental stress to alcoholism vulnerability.

    PubMed

    Campbell, Joannalee C; Szumlinski, Karen K; Kippin, Tod E

    2009-11-01

    The most problematic aspects of alcohol abuse disorder are excessive alcohol consumption and the inability to refrain from alcohol consumption during attempted abstinence. The root causes that predispose certain individuals to these problems are poorly understood but are believed to be produced by a combination of genetic and environmental factors. Early environmental trauma alters neurodevelopmental trajectories that can predispose an individual to a number of neuropsychiatric disorders, including substance abuse. Prenatal stress (PNS) is a well-established protocol that produces perturbations in nervous system development, resulting in behavioral alterations that include hyperresponsiveness to stress, novelty, and psychomotor stimulant drugs (e.g., cocaine, amphetamine). Moreover, PNS animals exhibit enduring alterations in basal and cocaine-induced changes in dopamine and glutamate transmission within limbic structures, which exhibit pathology in drug addiction and alcoholism, suggesting that these alterations may contribute to an increased propensity to self-administer large amounts of drugs of abuse or to relapse after periods of drug withdrawal. Given that cocaine and alcohol have actions on common limbic neural substrates (albeit by different mechanisms), we hypothesized that PNS would elevate the motivation for, and consumption of, alcohol. Accordingly, we have found that male C57BL/6J mice subject to PNS exhibit higher operant responding and consume more alcohol during alcohol reinforcement as adults. Alterations in glutamate and dopamine neurotransmission within the forebrain structures appear to contribute to the PNS-induced predisposition to high alcohol intake and are induced by excessive alcohol intake. Accordingly, we are exploring the interactions between neurochemical changes produced by PNS and changes induced by consumption of alcohol in adulthood to model the biological bases of high vulnerability to alcohol abuse.

  13. Contribution of early environmental stress to alcoholism vulnerability

    PubMed Central

    Campbell, Joannalee C.; Szumlinski, Karen K.; Kippin, Tod E.

    2011-01-01

    The most problematic aspects of alcohol abuse disorder are excessive alcohol consumption and the inability to refrain from alcohol consumption during attempted abstinence. The root causes that predispose certain individuals to these problems are poorly understood but are believed to be produced by a combination of genetic and environmental factors. Early environmental trauma alters neurodevelopmental trajectories that can predispose an individual to a number of neuropsychiatric disorders, including substance abuse. Prenatal stress (PNS) is a well-established protocol that produces perturbations in nervous system development, resulting in behavioral alterations that include hyperresponsiveness to stress, novelty, and psychomotor stimulant drugs (e.g., cocaine, amphetamine). Moreover, PNS animals exhibit enduring alterations in basal and cocaine-induced changes in dopamine and glutamate transmission within limbic structures, which exhibit pathology in drug addiction and alcoholism, suggesting that these alterations may contribute to an increased propensity to self-administer large amounts of drugs of abuse or to relapse after periods of drug withdrawal. Given that cocaine and alcohol have actions on common limbic neural substrates (albeit by different mechanisms), we hypothesized that PNS would elevate the motivation for, and consumption of, alcohol. Accordingly, we have found that male C57BL/6J mice subject to PNS exhibit higher operant responding and consume more alcohol during alcohol reinforcement as adults. Alterations in glutamate and dopamine neurotransmission within the forebrain structures appear to contribute to the PNS-induced predisposition to high alcohol intake and are induced by excessive alcohol intake. Accordingly, we are exploring the interactions between neurochemical changes produced by PNS and changes induced by consumption of alcohol in adulthood to model the biological bases of high vulnerability to alcohol abuse. PMID:19913199

  14. Persistent escalation of alcohol drinking in C57BL/6J mice with intermittent access to 20% ethanol.

    PubMed

    Hwa, Lara S; Chu, Adam; Levinson, Sally A; Kayyali, Tala M; DeBold, Joseph F; Miczek, Klaus A

    2011-11-01

    Intermittent access (IA) to drugs of abuse, as opposed to continuous access, is hypothesized to induce a kindling-type transition from moderate to escalated use, leading to dependence. Intermittent 24-hour cycles of ethanol access and deprivation can generate high levels of voluntary ethanol drinking in rats. The current study uses C57BL/6J mice (B6) in an IA to 20% ethanol protocol to escalate ethanol drinking levels. Adult male and female B6 mice were given IA to 20% ethanol on alternating days of the week with water available ad libitum. Ethanol consumption during the initial 2 hours of access was compared with a short-term, limited access "binge" drinking procedure, similar to drinking-in-the-dark (DID). B6 mice were also assessed for ethanol dependence with handling-induced convulsion, a reliable measure of withdrawal severity. After 3 weeks, male mice given IA to ethanol achieved high stable levels of ethanol drinking in excess of 20 g/kg/24 h, reaching above 100 mg/dl blood ethanol concentrations, and showed a significantly higher ethanol preference than mice given continuous access to ethanol. Also, mice given IA drank about twice as much as DID mice in the initial 2-hour access period. B6 mice that underwent the IA protocol for longer periods of time displayed more severe signs of alcohol withdrawal. Additionally, female B6 mice were given IA to ethanol and drank significantly more than males (ca. 30 g/kg/24 h). The IA method in B6 mice is advantageous because it induces escalated, voluntary, and preferential per os ethanol intake, behavior that may mimic a cardinal feature of human alcohol dependence, though the exact nature and site of ethanol acting in the brain and blood as a result of IA has yet to be determined. Copyright © 2011 by the Research Society on Alcoholism.

  15. Levels of Social Sharing and Clinical Implications for Severe Social Withdrawal in Patients with Personality Disorders

    PubMed Central

    Colle, Livia; Pellecchia, Giovanni; Moroni, Fabio; Carcione, Antonino; Nicolò, Giuseppe; Semerari, Antonio; Procacci, Michele

    2017-01-01

    Social sharing capacities have attracted attention from a number of fields of social cognition and have been variously defined and analyzed in numerous studies. Social sharing consists in the subjective awareness that aspects of the self’s experience are held in common with other individuals. The definition of social sharing must take a variety of elements into consideration: the motivational element, the contents of the social sharing experience, the emotional responses it evokes, the behavioral outcomes, and finally, the circumstances and the skills which enable social sharing. The primary objective of this study is to explore some of the diverse forms of human social sharing and to classify them according to levels of complexity. We identify four different types of social sharing, categorized according to the nature of the content being shared and the complexity of the mindreading skills required. The second objective of this study is to consider possible applications of this graded model of social sharing experience in clinical settings. Specifically, this model may support the development of graded, focused clinical interventions for patients with personality disorders characterized by severe social withdrawal. PMID:29255430

  16. 5 CFR 362.407 - Withdrawal and readmission.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Withdrawal and readmission. 362.407 Section 362.407 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS PROGRAMS Presidential Management Fellows Program § 362.407 Withdrawal and readmission. (a) Withdrawal. (1...

  17. 5 CFR 362.407 - Withdrawal and readmission.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Withdrawal and readmission. 362.407 Section 362.407 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS PROGRAMS Presidential Management Fellows Program § 362.407 Withdrawal and readmission. (a) Withdrawal. (1...

  18. Alcohol Content in the 'Hyper-Reality' MTV Show 'Geordie Shore'.

    PubMed

    Lowe, Eden; Britton, John; Cranwell, Jo

    2018-05-01

    To quantify the occurrence of alcohol content, including alcohol branding, in the popular primetime television UK Reality TV show 'Geordie Shore' Series 11. A 1-min interval coding content analysis of alcohol content in the entire DVD Series 11 of 'Geordie Shore' (10 episodes). Occurrence of alcohol use, implied use, other alcohol reference/paraphernalia or branding was recorded. All categories of alcohol were present in all episodes. 'Any alcohol' content occurred in 78%, 'actual alcohol use' in 30%, 'inferred alcohol use' in 72%, and all 'other' alcohol references occurred in 59% of all coding intervals (ACIs), respectively. Brand appearances occurred in 23% of ACIs. The most frequently observed alcohol brand was Smirnoff which appeared in 43% of all brand appearances. Episodes categorized as suitable for viewing by adolescents below the legal drinking age of 18 years comprised of 61% of all brand appearances. Alcohol content, including branding, is highly prevalent in the UK Reality TV show 'Geordie Shore' Series 11. Two-thirds of all alcohol branding occurred in episodes age-rated by the British Board of Film Classification (BBFC) as suitable for viewers aged 15 years. The organizations OfCom, Advertising Standards Authority (ASA) and the Portman Group should implement more effective policies to reduce adolescent exposure to on-screen drinking. The drinks industry should consider demanding the withdrawal of their brands from the show. Alcohol content, including branding, is highly prevalent in the MTV reality TV show 'Geordie Shore' Series 11. Current alcohol regulation is failing to protect young viewers from exposure to such content.

  19. Effect of Nimodipine on Morphine-related Withdrawal Syndrome in Rat Model: An Observational Study

    PubMed Central

    Mishra, Pravash Ranjan; Barik, Mayadhar; Ray, Subrata Basu

    2017-01-01

    Objective: To observe the effect of L-type calcium channel blocker like nimodipine on morphine's withdrawal when it was administered continuously along with morphine versus a single bolus dose of nimodipine, which was administered at the end of the experiment before the precipitation of withdrawal reaction in morphine-dependent rats. Materials and Methods: Four groups of adult male Wistar rats were rendered morphine dependent by subcutaneous injections of morphine at a dose of 10 mg/kg for 10 days. Nimodipine 10 mg/kg intraperitoneally (ip) administered to one group once daily before morphine administration in the entire experimental period, and another group received nimodipine only once at the end of the experiment as a single bolus dose 2 mg/kg before the administration of naloxone. Naloxone 3 mg/kg was administered ip to all the groups to precipitate withdrawal reactions. The withdrawal reactions were evaluated and scored as per the Gellert and Holtzman global withdrawal rating scale. Results: Nimodipine when administered as a single bolus dose before naloxone administration in morphine-dependant rats reduced the features of withdrawal reactions more effectively than continuous administration of nimodipine along with morphine throughout the experimental period. Conclusion: We discovered that nimodipine helps in attenuating the severity of morphine withdrawal having potential role encountered during pharmacotherapy with morphine management of opioid dependence, well memory, impairement, cell signaling and phosphorylation of neuron. PMID:28553371

  20. Effect of Nimodipine on Morphine-related Withdrawal Syndrome in Rat Model: An Observational Study.

    PubMed

    Mishra, Pravash Ranjan; Barik, Mayadhar; Ray, Subrata Basu

    2017-01-01

    To observe the effect of L-type calcium channel blocker like nimodipine on morphine's withdrawal when it was administered continuously along with morphine versus a single bolus dose of nimodipine, which was administered at the end of the experiment before the precipitation of withdrawal reaction in morphine-dependent rats. Four groups of adult male Wistar rats were rendered morphine dependent by subcutaneous injections of morphine at a dose of 10 mg/kg for 10 days. Nimodipine 10 mg/kg intraperitoneally (ip) administered to one group once daily before morphine administration in the entire experimental period, and another group received nimodipine only once at the end of the experiment as a single bolus dose 2 mg/kg before the administration of naloxone. Naloxone 3 mg/kg was administered ip to all the groups to precipitate withdrawal reactions. The withdrawal reactions were evaluated and scored as per the Gellert and Holtzman global withdrawal rating scale. Nimodipine when administered as a single bolus dose before naloxone administration in morphine-dependant rats reduced the features of withdrawal reactions more effectively than continuous administration of nimodipine along with morphine throughout the experimental period. We discovered that nimodipine helps in attenuating the severity of morphine withdrawal having potential role encountered during pharmacotherapy with morphine management of opioid dependence, well memory, impairement, cell signaling and phosphorylation of neuron.

  1. 19 CFR 144.27 - Withdrawal from warehouse by transferee.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...; DEPARTMENT OF THE TREASURY (CONTINUED) WAREHOUSE AND REWAREHOUSE ENTRIES AND WITHDRAWALS Transfer of Right To Withdraw Merchandise from Warehouse § 144.27 Withdrawal from warehouse by transferee. At any time within... withdraw all or part of the merchandise covered by the transfer by filing any authorized kind of withdrawal...

  2. 19 CFR 144.27 - Withdrawal from warehouse by transferee.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...; DEPARTMENT OF THE TREASURY (CONTINUED) WAREHOUSE AND REWAREHOUSE ENTRIES AND WITHDRAWALS Transfer of Right To Withdraw Merchandise from Warehouse § 144.27 Withdrawal from warehouse by transferee. At any time within... withdraw all or part of the merchandise covered by the transfer by filing any authorized kind of withdrawal...

  3. Cerebral blood flow and oxygen consumption during ethanol withdrawal in the rat.

    PubMed

    Hemmingsen, R; Barry, D I; Hertz, M M; Klinken, L

    1979-09-14

    The ethanol withdrawal syndrome in man and animals is characterized by signs of CNS hyperactivity although a direct measurement of a physiological variable reflecting this CNS hyperactivity has never been performed in untreated man or in animals. We induced ethanol dependence in the rat by means of intragastric intubation with a 20% w/v ethanol solution, thus keeping the animals in a state of continuous severe intoxication for 3--4 days; during the subsequent state of withdrawal characterized by tremor, rigidity, stereotyped movements and general seizures a 25% increase in cerebral oxygen consumption (CMRO2) could be measured; this increase was not due to catecholamines originating from adrenal medulla as adrenomedullectomized animals showed a similar increase in CMRO2 (28%); the withdrawing animals showed a corresponding cerebral blood flow (CBF) increase. The elevated CMRO2 and CBF could be reduced to normal by administration of a beta-adrenergic receptor blocker (propranolol 2 mg/kg i.v.), and hence the increased CMRO2 during ethanol withdrawal could be related to catecholaminergic systems in the brain, e.g. the noradrenergic locus coeruleus system which is anatomically well suited as a general activating system. This interpretation is supported by the earlier neurochemical finding of an increased cerebral noradrenaline turnover during ethanol withdrawal. The exact mechanism underlying the increased cerebral oxygen consumption during ethanol withdrawal and the effect of propranolol on cerebral function during this condition remains to be clarified.

  4. New mechanisms and perspectives in nicotine withdrawal

    PubMed Central

    Jackson, K.J.; Muldoon, P.P.; De Biasi, M.; Damaj, M.I.

    2014-01-01

    Diseases associated with tobacco use constitute a major health problem worldwide. Upon cessation of tobacco use, an unpleasant withdrawal syndrome occurs in dependent individuals. Avoidance of the negative state produced by nicotine withdrawal represents a motivational component that promotes continued tobacco use and relapse after smoking cessation. With the modest success rate of currently available smoking cessation therapies, understanding mechanisms involved in the nicotine withdrawal syndrome are crucial for developing successful treatments. Animal models provide a useful tool for examining neuroadaptative mechanisms and factors influencing nicotine withdrawal, including sex, age, and genetic factors. Such research has also identified an important role for nicotinic receptor subtypes in different aspects of the nicotine withdrawal syndrome (e.g., physical vs. affective signs). In addition to nicotinic receptors, the opioid and endocannabinoid systems, various signal transduction pathways, neurotransmitters, and neuropeptides have been implicated in the nicotine withdrawal syndrome. Animal studies have informed human studies of genetic variants and potential targets for smoking cessation therapies. Overall, the available literature indicates that the nicotine withdrawal syndrome is complex, and involves a range of neurobiological mechanisms. As research in nicotine withdrawal progresses, new pharmacological options for smokers attempting to quit can be identified, and treatments with fewer side effects that are better tailored to the unique characteristics of patients may become available. PMID:25433149

  5. Perspectives on the neuroscience of alcohol from the National Institute on Alcohol Abuse and Alcoholism.

    PubMed

    Reilly, Matthew T; Noronha, Antonio; Warren, Kenneth

    2014-01-01

    Mounting evidence over the last 40 years clearly indicates that alcoholism (alcohol dependence) is a disorder of the brain. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has taken significant steps to advance research into the neuroscience of alcohol. The Division of Neuroscience and Behavior (DNB) was formed within NIAAA in 2002 to oversee, fund, and direct all research areas that examine the effects of alcohol on the brain, the genetic underpinnings of alcohol dependence, the neuroadaptations resulting from excessive alcohol consumption, advanced behavioral models of the various stages of the addiction cycle, and preclinical medications development. This research portfolio has produced important discoveries in the etiology, treatment, and prevention of alcohol abuse and dependence. Several of these salient discoveries are highlighted and future areas of neuroscience research on alcohol are presented. © 2014 Elsevier B.V. All rights reserved.

  6. Timing of nicotine lozenge administration to minimize trigger induced craving and withdrawal symptoms.

    PubMed

    Kotlyar, Michael; Lindgren, Bruce R; Vuchetich, John P; Le, Chap; Mills, Anne M; Amiot, Elizabeth; Hatsukami, Dorothy K

    2017-08-01

    Smokers are often advised to use nicotine lozenge when craving or withdrawal symptoms occur. This may be too late to prevent lapses. This study assessed if nicotine lozenge use prior to a common smoking trigger can minimize trigger induced increases in craving and withdrawal symptoms. Eighty-four smokers completed two laboratory sessions in random order. At one session, nicotine lozenge was given immediately after a stressor (to approximate current recommended use - i.e., after craving and withdrawal symptoms occur); at the other session subjects were randomized to receive nicotine lozenge at time points ranging from immediately to 30min prior to the stressor. Withdrawal symptoms and urge to smoke were measured using the Minnesota Nicotine Withdrawal Scale and the Questionnaire of Smoking Urges (QSU). Relative to receiving lozenge after the stressor, a smaller increase in pre-stressor to post-stressor withdrawal symptom scores occurred when lozenge was used immediately (p=0.03) and 10min prior (p=0.044) to the stressor. Results were similar for factors 1 and 2 of the QSU when lozenge was used immediately prior to the stressor (p<0.03) and for factor 1 of the QSU when lozenge was used 10min prior to the stressor (p=0.028). Absolute levels of post-stressor withdrawal symptom and urge to smoke severity were lower when lozenge was given prior to versus after a stressor. Administering the nicotine lozenge prior to a smoking trigger can decrease trigger induced craving and withdrawal symptoms. Future studies are needed to determine if such use would increase cessation rates. Clinicaltrials.gov # NCT01522963. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Alcohol-induced tolerance and physical dependence in mice with ethanol insensitive α1 GABAA receptors

    PubMed Central

    Werner, David F.; Swihart, Andrew R.; Ferguson, Carolyn; Lariviere, William R.; Harrison, Neil L.; Homanics, Gregg E.

    2009-01-01

    Background Although many people consume alcohol (ethanol), it remains unknown why some become addicted. Elucidating the molecular mechanisms of tolerance and physical dependence (withdrawal) may provide insight into alcohol addiction. While the exact molecular mechanisms of ethanol action are unclear, γ-aminobutyric acid type A receptors (GABAA-Rs) have been extensively implicated in ethanol action. The α1 GABAA-R subunit is associated with tolerance and physical dependence, but its exact role remains unknown. In this report, we tested the hypothesis that α1-GABAA-Rs mediate in part these effects of ethanol. Methods Ethanol-induced behavioral responses related to tolerance and physical dependence were investigated in knockin mice that have ethanol-insensitive α1 GABAA-Rs and wildtype controls. Acute functional tolerance (AFT) was assessed using the stationary dowel and loss of righting reflex assays. Chronic tolerance was assessed on the loss of righting reflex, fixed speed rotarod, hypothermia, and radiant tail flick assays following ten consecutive days of ethanol exposure. Withdrawal-related hyperexcitability was assessed by handling-induced convulsions following 3 cycles of ethanol vapor exposure/withdrawal. Immunoblots were used to assess α1 protein levels. Results Compared to controls, knockin mice displayed decreased AFT and chronic tolerance to ethanol-induced motor ataxia, and also displayed heightened ethanol-withdrawal hyperexcitability. No differences between wildtype and knockin mice were seen in other ethanol-induced behavioral measures. Following chronic exposure to ethanol, control mice displayed reductions in α1 protein levels, but knockins did not. Conclusions We conclude that α1-GABAA-Rs play a role in tolerance to ethanol-induced motor ataxia and withdrawal-related hyperexcitability. However, other aspects of behavioral tolerance and physical dependence do not rely on α1-containing GABAA-Rs. PMID:19032579

  8. 29 CFR 4219.12 - Employers liable upon mass withdrawal.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Employers liable upon mass withdrawal. 4219.12 Section 4219... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.12 Employers liable upon mass withdrawal. (a... experiences successive mass withdrawals, an employer that has been determined to be liable under this subpart...

  9. 29 CFR 4219.12 - Employers liable upon mass withdrawal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 9 2011-07-01 2011-07-01 false Employers liable upon mass withdrawal. 4219.12 Section 4219... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.12 Employers liable upon mass withdrawal. (a... experiences successive mass withdrawals, an employer that has been determined to be liable under this subpart...

  10. Neural correlates of instrumental responding in the context of alcohol-related cues index disorder severity and relapse risk.

    PubMed

    Schad, Daniel J; Garbusow, Maria; Friedel, Eva; Sommer, Christian; Sebold, Miriam; Hägele, Claudia; Bernhardt, Nadine; Nebe, Stephan; Kuitunen-Paul, Sören; Liu, Shuyan; Eichmann, Uta; Beck, Anne; Wittchen, Hans-Ulrich; Walter, Henrik; Sterzer, Philipp; Zimmermann, Ulrich S; Smolka, Michael N; Schlagenhauf, Florian; Huys, Quentin J M; Heinz, Andreas; Rapp, Michael A

    2018-01-08

    The influence of Pavlovian conditioned stimuli on ongoing behavior may contribute to explaining how alcohol cues stimulate drug seeking and intake. Using a Pavlovian-instrumental transfer task, we investigated the effects of alcohol-related cues on approach behavior (i.e., instrumental response behavior) and its neural correlates, and related both to the relapse after detoxification in alcohol-dependent patients. Thirty-one recently detoxified alcohol-dependent patients and 24 healthy controls underwent instrumental training, where approach or non-approach towards initially neutral stimuli was reinforced by monetary incentives. Approach behavior was tested during extinction with either alcohol-related or neutral stimuli (as Pavlovian cues) presented in the background during functional magnetic resonance imaging (fMRI). Patients were subsequently followed up for 6 months. We observed that alcohol-related background stimuli inhibited the approach behavior in detoxified alcohol-dependent patients (t = - 3.86, p < .001), but not in healthy controls (t = - 0.92, p = .36). This behavioral inhibition was associated with neural activation in the nucleus accumbens (NAcc) (t (30)  = 2.06, p < .05). Interestingly, both the effects were only present in subsequent abstainers, but not relapsers and in those with mild but not severe dependence. Our data show that alcohol-related cues can acquire inhibitory behavioral features typical of aversive stimuli despite being accompanied by a stronger NAcc activation, suggesting salience attribution. The fact that these findings are restricted to abstinence and milder illness suggests that they may be potential resilience factors. LeAD study, http://www.lead-studie.de , NCT01679145.

  11. Factors Influencing Injury Severity of Bicyclists Involved in Crashes with Motor Vehicles: Bike Lanes, Alcohol, Lighting, Speed, and Helmet Use.

    PubMed

    Helak, Kelsey; Jehle, Dietrich; McNabb, Daniel; Battisti, Amanda; Sanford, Steward; Lark, Mary Claire

    2017-07-01

    In 2014, 726 bicyclists were killed and an additional 50,000 were injured in crashes with motor vehicles. The number of cyclists in the United States is increasing, and as a result there has been a call for more bike lanes. We examined the difference in the severity of injury of bicyclists involved in motor vehicle crashes when riding in the traffic lane compared with riding in a bike lane or on a paved shoulder. We also controlled for other safety factors, including alcohol use, travel speed, posted speed, helmet usage, and lighting conditions to determine their impact on bicyclist safety. Single-year National Automotive Sampling System-General Estimates System files were used to analyze data regarding the bike lanes, and multiyear data were used to analyze the additional factors. Univariate and multiple regression analyses controlling for confounders were performed on the data. When adjusting for speed limit, alcohol use by driver, weather conditions, time of day, and helmet use, the cyclist's position had no significant effect on the severity of injury ( P = 0.57). The severity of injury was significantly greater when the driver or bicyclist had been drinking alcohol ( P < 0.0001 and P < 0.003, respectively). Bicyclists were more severely injured when vehicles moved at greater speeds and the posted speed limit was higher ( P < 0.0001 for both). Also, injury severity was found to be significantly higher when lighting conditions were "dark" ( P < 0.0001). Our findings suggest that simply having a dedicated space for bicyclists, such as a bike lane or a paved shoulder, does not reduce the severity of injuries sustained when a crash with a motor vehicle takes place. Cyclist safety could be improved by implementing changes that affect vehicle speed, alcohol use by drivers, and lighting conditions. Moreover, emergency physicians should be aware that when they receive a report of a cyclist being struck by a car in a bike lane, they should prepare to treat injuries of

  12. Changes in the female arcuate nucleus morphology and neurochemistry after chronic ethanol consumption and long-term withdrawal.

    PubMed

    Rebouças, Elce C C; Leal, Sandra; Silva, Susana M; Sá, Susana I

    2016-11-01

    Ethanol is a macronutrient whose intake is a form of ingestive behavior, sharing physiological mechanisms with food intake. Chronic ethanol consumption is detrimental to the brain, inducing gender-dependent neuronal damage. The hypothalamic arcuate nucleus (ARN) is a modulator of food intake that expresses feeding-regulatory neuropeptides, such as alpha melanocyte-stimulating hormone (α-MSH) and neuropeptide Y (NPY). Despite its involvement in pathways associated with eating disorders and ethanol abuse, the impact of ethanol consumption and withdrawal in the ARN structure and neurochemistry in females is unknown. We used female rat models of 20% ethanol consumption for six months and of subsequent ethanol withdrawal for two months. Food intake and body weights were measured. ARN morphology was stereologically analyzed to estimate its volume, total number of neurons and total number of neurons expressing NPY, α-MSH, tyrosine hydroxylase (TH) and estrogen receptor alpha (ERα). Ethanol decreased energy intake and body weights. However, it did not change the ARN morphology or the expression of NPY, α-MSH and TH, while increasing ERα expression. Withdrawal induced a significant volume and neuron loss that was accompanied by an increase in NPY expression without affecting α-MSH and TH expression. These findings indicate that the female ARN is more vulnerable to withdrawal than to excess alcohol. The data also support the hypothesis that the same pathways that regulate the expression of NPY and α-MSH in long-term ethanol intake may regulate food intake. The present model of long-term ethanol intake and withdrawal induces new physiological conditions with adaptive responses. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. 29 CFR 1626.13 - Withdrawal of charge.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 4 2012-07-01 2012-07-01 false Withdrawal of charge. 1626.13 Section 1626.13 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION PROCEDURES-AGE DISCRIMINATION IN EMPLOYMENT ACT § 1626.13 Withdrawal of charge. Charging parties may request withdrawal of a...

  14. 29 CFR 1626.13 - Withdrawal of charge.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Withdrawal of charge. 1626.13 Section 1626.13 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION PROCEDURES-AGE DISCRIMINATION IN EMPLOYMENT ACT § 1626.13 Withdrawal of charge. Charging parties may request withdrawal of a...

  15. 29 CFR 1626.13 - Withdrawal of charge.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 4 2013-07-01 2013-07-01 false Withdrawal of charge. 1626.13 Section 1626.13 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION PROCEDURES-AGE DISCRIMINATION IN EMPLOYMENT ACT § 1626.13 Withdrawal of charge. Charging parties may request withdrawal of a...

  16. 29 CFR 1626.13 - Withdrawal of charge.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 4 2014-07-01 2014-07-01 false Withdrawal of charge. 1626.13 Section 1626.13 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION PROCEDURES-AGE DISCRIMINATION IN EMPLOYMENT ACT § 1626.13 Withdrawal of charge. Charging parties may request withdrawal of a...

  17. 29 CFR 1626.13 - Withdrawal of charge.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 4 2011-07-01 2011-07-01 false Withdrawal of charge. 1626.13 Section 1626.13 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION PROCEDURES-AGE DISCRIMINATION IN EMPLOYMENT ACT § 1626.13 Withdrawal of charge. Charging parties may request withdrawal of a...

  18. 21 CFR 870.1800 - Withdrawal-infusion pump.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Withdrawal-infusion pump. 870.1800 Section 870...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Diagnostic Devices § 870.1800 Withdrawal-infusion pump. (a) Identification. A withdrawal-infusion pump is a device designed to inject accurately drugs...

  19. Cross-commodity delay discounting of alcohol and money in alcohol users

    PubMed Central

    Moody, Lara N.; Tegge, Allison N.; Bickel, Warren K.

    2017-01-01

    Despite real-world implications, the pattern of delay discounting in alcohol users when the commodities now and later differ has not been well characterized. In this study, 60 participants on Amazon's Mechanical Turk completed the Alcohol Use Disorder Identification Test (AUDIT) to assess severity of use and completed four delay discounting tasks between hypothetical, equivalent amounts of alcohol and money available at five delays. The tasks included two cross-commodity (alcohol now-money later and money now-alcohol later) and two same-commodity (money now-money later and alcohol now-alcohol later) conditions. Delay discounting was significantly associated with clinical cutoffs of the AUDIT for both of the cross-commodity conditions but not for either of the same-commodity delay discounting tasks. The cross-commodity discounting conditions were related to severity of use wherein heavy users discounted future alcohol less and future money more. The change in direction of the discounting effect was dependent on the commodity that was distally available suggesting a distinctive pattern of discounting across commodities when comparing light and heavy alcohol users. PMID:29056767

  20. Cross-commodity delay discounting of alcohol and money in alcohol users.

    PubMed

    Moody, Lara N; Tegge, Allison N; Bickel, Warren K

    2017-06-01

    Despite real-world implications, the pattern of delay discounting in alcohol users when the commodities now and later differ has not been well characterized. In this study, 60 participants on Amazon's Mechanical Turk completed the Alcohol Use Disorder Identification Test (AUDIT) to assess severity of use and completed four delay discounting tasks between hypothetical, equivalent amounts of alcohol and money available at five delays. The tasks included two cross-commodity (alcohol now-money later and money now-alcohol later) and two same-commodity (money now-money later and alcohol now-alcohol later) conditions. Delay discounting was significantly associated with clinical cutoffs of the AUDIT for both of the cross-commodity conditions but not for either of the same-commodity delay discounting tasks. The cross-commodity discounting conditions were related to severity of use wherein heavy users discounted future alcohol less and future money more. The change in direction of the discounting effect was dependent on the commodity that was distally available suggesting a distinctive pattern of discounting across commodities when comparing light and heavy alcohol users.

  1. Bacterial meningitis in alcoholic patients: A population-based prospective study.

    PubMed

    van Veen, Kiril E B; Brouwer, Matthijs C; van der Ende, Arie; van de Beek, Diederik

    2017-04-01

    To study clinical features and outcome of community-acquired bacterial meningitis in alcoholic patients. Patients with a history of alcoholism were selected from our nationwide, prospective cohort on community-acquired bacterial meningitis performed from March 2006 to October 2014. Data on patient history, symptoms and signs on admission, treatment, and outcome were prospectively collected. Of 1359 included episodes, 88 episodes (6%) occurred in 88 alcoholic patients. Seizures as presenting symptom were present in 18% alcoholic patients, and 23% presented with co-existing pneumonia. Causative organisms were Streptococcus pneumoniae in 76%, Listeria monocytogenes in 8%, and Neisseria meningitidis in 6% of patients. A high rate of systemic complications occurred with respiratory failure in 40% and endocarditis in 9% of patients. Outcome was unfavorable in 58% of alcoholic patients, and 25% died. Alcoholism was associated with unfavorable outcome in a multivariate analysis (OR 1.96; 95% CI 1.12-3.46; P = 0.019), but not with death (OR 0.76; 95% CI 0.35-1.68; P = 0.762). Alcoholic bacterial meningitis patients often have an unfavorable outcome, which appears to result from a high rate of systemic complications, mainly respiratory failure. Seizures are common in alcoholic patients and warrant caution of development of an alcohol withdrawal syndrome. Copyright © 2017. Published by Elsevier Ltd.

  2. 47 CFR 1.8 - Withdrawal of papers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false Withdrawal of papers. 1.8 Section 1.8 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE General Rules of Practice and Procedure General § 1.8 Withdrawal of papers. The granting of a request to dismiss or withdraw an...

  3. 47 CFR 1.8 - Withdrawal of papers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Withdrawal of papers. 1.8 Section 1.8 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE General Rules of Practice and Procedure General § 1.8 Withdrawal of papers. The granting of a request to dismiss or withdraw an...

  4. Alcoholic and non-alcoholic steatohepatitis

    PubMed Central

    Neuman, Manuela G.; French, Samuel W.; French, Barbara A.; Seitz, Helmut K.; Cohen, Lawrence B.; Mueller, Sebastian; Osna, Natalia A.; Kharbanda, Kusum K.; Seth, Devanshi; Bautista, Abraham; Thompson, Kyle J.; McKillop, Iain H.; Kirpich, Irina A.; McClain, Craig J.; Bataller, Ramon; Nanau, Radu M.; Voiculescu, Mihai; Opris, Mihai; Shen, Hong; Tillman, Brittany; Li, Jun; Liu, Hui; Thomas, Paul G.; Ganesan, Murali; Malnick, Steve

    2015-01-01

    This paper is based upon the “Charles Lieber Satellite Symposia” organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its comorbidities with chronic viral hepatitis in the presence or absence of human deficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible

  5. Effects of chronic morphine and morphine withdrawal on gene expression in rat peripheral blood mononuclear cells.

    PubMed

    Desjardins, Stephane; Belkai, Emilie; Crete, Dominique; Cordonnier, Laurie; Scherrmann, Jean-Michel; Noble, Florence; Marie-Claire, Cynthia

    2008-12-01

    Chronic morphine treatment alters gene expression in brain structures. There are increasing evidences showing a correlation, in gene expression modulation, between blood cells and brain in psychological troubles. To test whether gene expression regulation in blood cells could be found in drug addiction, we investigated gene expression profiles in peripheral blood mononuclear (PBMC) cells of saline and morphine-treated rats. In rats chronically treated with morphine, the behavioral signs of spontaneous withdrawal were observed and a withdrawal score was determined. This score enabled to select the time points at which the animals displayed the mildest and strongest withdrawal signs (12 h and 36 h after the last injection). Oligonucleotide arrays were used to assess differential gene expression in the PBMCs and quantitative real-time RT-PCR to validate the modulation of several candidate genes 12 h and 36 h after the last injection. Among the 812 differentially expressed candidates, several genes (Adcy5, Htr2a) and pathways (Map kinases, G-proteins, integrins) have already been described as modulated in the brain of morphine-treated rats. Sixteen out of the twenty-four tested candidates were validated at 12 h, some of them showed a sustained modulation at 36 h while for most of them the modulation evolved as the withdrawal score increased. This study suggests similarities between the gene expression profile in PBMCs and brain of morphine-treated rats. Thus, the searching of correlations between the severity of the withdrawal and the PBMCs gene expression pattern by transcriptional analysis of blood cells could be promising for the study of the mechanisms of addiction.

  6. 19 CFR 144.36 - Withdrawal for transportation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Withdrawal for transportation. 144.36 Section 144... § 144.36 Withdrawal for transportation. (a) Time limit. Merchandise may be withdrawn from warehouse for transportation to another port of entry if withdrawal for consumption or exportation can be accomplished at the...

  7. 19 CFR 144.36 - Withdrawal for transportation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 2 2013-04-01 2013-04-01 false Withdrawal for transportation. 144.36 Section 144... § 144.36 Withdrawal for transportation. (a) Time limit. Merchandise may be withdrawn from warehouse for transportation to another port of entry if withdrawal for consumption or exportation can be accomplished at the...

  8. 19 CFR 144.36 - Withdrawal for transportation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 2 2011-04-01 2011-04-01 false Withdrawal for transportation. 144.36 Section 144... § 144.36 Withdrawal for transportation. (a) Time limit. Merchandise may be withdrawn from warehouse for transportation to another port of entry if withdrawal for consumption or exportation can be accomplished at the...

  9. 19 CFR 144.36 - Withdrawal for transportation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 2 2012-04-01 2012-04-01 false Withdrawal for transportation. 144.36 Section 144... § 144.36 Withdrawal for transportation. (a) Time limit. Merchandise may be withdrawn from warehouse for transportation to another port of entry if withdrawal for consumption or exportation can be accomplished at the...

  10. Cigarette craving and withdrawal symptoms during temporary abstinence and the effect of nicotine gum.

    PubMed

    Brown, Jamie; Hajek, Peter; McRobbie, Hayden; Locker, Jo; Gillison, Fiona; McEwen, Andy; Beard, Emma; West, Robert

    2013-09-01

    It is widely believed that nicotine withdrawal symptoms appear within a few hours of stopping smoking, but few data exist documenting their emergence in naturalistic settings. In several countries, nicotine replacement products are licensed for relief of withdrawal symptoms during temporary abstinence, but again, there are no data supporting this from naturalistic settings. To examine the emergence of cigarette craving and withdrawal symptoms during temporary abstinence in a naturalistic setting while using either nicotine or placebo gum. Double-blind, randomised, placebo-controlled study in which 132 dependent smokers abstained for 6 h with the assistance of either nicotine (2 mg, n = 42 or 4 mg, n = 24) or placebo (n = 66) gum while travelling on a non-smoking train. Outcome measures were ratings of craving and mood withdrawal symptoms prior to treatment and at regular intervals during abstinence. In a multivariate analysis of all symptoms, there was no interaction between treatment and time [F(21,110) = 1.28, p = 0.20, η²(p)= 0.20] nor an effect of treatment [F(7,124) = 0.45, p = 0.87, η²(p)=  0.03]. There was an effect of time [F(21,110) = 11.59, p < 0.001, η²(p)= 0.69) and univariate analyses revealed that the majority of symptoms increased linearly throughout the period of abstinence with detectable onsets typically between the first 60 and 180 min of abstinence. Smokers who temporarily abstain in naturalistic settings experience craving and withdrawal symptoms that emerge linearly over the first 6 h of abstinence. Changes in craving and several mood withdrawal symptoms can be detected within the first 3 h. Nicotine gum may not have an acute effect on the development of these symptoms.

  11. Altering ethanol pharmacokinetics to treat alcohol use disorder: Can you teach an old dog new tricks?

    PubMed

    Haass-Koffler, Carolina L; Akhlaghi, Fatemeh; Swift, Robert M; Leggio, Lorenzo

    2017-07-01

    Disulfiram was the first pharmacotherapy approved to treat alcohol use disorder in the 1950s. Disulfiram alters ethanol pharmacokinetics and causes uncomfortable reactions (e.g. headache, tachycardia, nausea, flushing and hypotension) when alcohol is consumed. Subsequently, a better understanding of the neurobiological pathways involved in alcohol use disorder led to the development of other medications (e.g. naltrexone and acamprosate). These neurobiological-based medications act on alcohol use disorder-related phenotypes including craving, stress, and/or withdrawal. The original approach to treat alcohol use disorder, by altering ethanol pharmacokinetics has been much less investigated. Recent research on ethanol pharmacokinetics has shed light on the mechanisms of action underlying alcohol use disorder and how some medications that alter ethanol pharmacokinetics may be helpful in treating alcohol use disorder. This review summarizes and discusses the complex pharmacokinetics of ethanol, and proposes that altering ethanol pharmacokinetics via novel pharmacological approaches may be a viable approach to treat alcohol use disorder.

  12. Ethanol induced adaptations in 5-HT2c receptor signaling in the bed nucleus of stria terminalis: Implications for anxiety during ethanol withdrawal

    PubMed Central

    Marcinkiewcz, Catherine A.; Dorrier, Cayce E.; Lopez, Alberto J.; Kash, Thomas L.

    2015-01-01

    One of the hallmarks of alcohol dependence is the presence of a withdrawal syndrome during abstinence, which manifests as physical craving for alcohol accompanied by subjective feelings of anxiety. Using a model of chronic intermittent ethanol (CIE) vapor in mice, we investigated the role of serotonin2c signaling in the BNST as a neural substrate underlying ethanol-induced anxiety during withdrawal. Mice were subjected to a 5-day CIE regimen of 16 hours of ethanol vapor exposure followed by an 8 hour “withdrawal” period between exposures. After the 5th and final exposure, mice were withdrawn for 24 hours or 1 week before experiments began. Anxiety-like behavior was assessed in the social approach, light dark, and open field test with mice showing deficits in social, but not general anxiety-like behavior that was alleviated by pretreatment with the 5HT2c-R antagonist SB 242,084 (3 mg/kg, i.p.) 24 hours and 1 week post-CIE. Using immunohistochemistry and whole cell patch clamp electrophysiology, we also found that CIE increased FOS-IR and enhanced neuronal excitability in the ventral BNST (vBNST) 24 hrs into withdrawal in a 5HT2c-R dependent manner. This enhanced excitability persisted for 1 week post-CIE. We also found that mCPP, a 5HT2c/b agonist, induced a more robust depolarization in cells of the vBNST in CIE mice, confirming that 5HT2c-R signaling is upregulated in the vBNST following CIE. Taken together, these results suggest that CIE upregulates 5HT2c-R signaling in the vBNST, leading to increased excitability. This enhanced excitability of the vBNST may drive increased anxiety-like behavior during ethanol withdrawal. PMID:25229718

  13. Nontraditional Student Withdrawal from Undergraduate Accounting Programmes: A Holistic Perspective

    ERIC Educational Resources Information Center

    Fortin, Anne; Sauvé, Louise; Viger, Chantal; Landry, France

    2016-01-01

    A collaborative project of several Quebec universities, this study investigates nontraditional student withdrawal from undergraduate accounting programmes. A nontraditional student is older than 24, or is a commuter or a part-time student, or combines some of these characteristics. Univariate and multivariate analyses of student dropout factors…

  14. Estimated freshwater withdrawals in Washington, 2010

    USGS Publications Warehouse

    Lane, Ron C.; Welch, Wendy B.

    2015-03-18

    The amount of public- and self-supplied water used for domestic, irrigation, livestock, aquaculture, industrial, mining, and thermoelectric power was estimated for state, county, and eastern and western regions of Washington during calendar year 2010. Withdrawals of freshwater for offstream uses were estimated to be about 4,885 million gallons per day. The total estimated freshwater withdrawals for 2010 was approximately 15 percent less than the 2005 estimate because of decreases in irrigation and thermoelectric power withdrawals.

  15. 19 CFR 144.38 - Withdrawal for consumption.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... provided in § 141.61(e) of this chapter. (b) Withdrawal for exportation to Canada or Mexico. A withdrawal... withdrawal of cigars, cigarettes, or cigarette papers or tubes subject to internal revenue tax, the statement... will be finally due upon liquidation. (e) Permit for release of merchandise. When the duties and other...

  16. 19 CFR 144.38 - Withdrawal for consumption.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... provided in § 141.61(e) of this chapter. (b) Withdrawal for exportation to Canada or Mexico. A withdrawal... withdrawal of cigars, cigarettes, or cigarette papers or tubes subject to internal revenue tax, the statement... will be finally due upon liquidation. (e) Permit for release of merchandise. When the duties and other...

  17. 19 CFR 144.38 - Withdrawal for consumption.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... provided in § 141.61(e) of this chapter. (b) Withdrawal for exportation to Canada or Mexico. A withdrawal... withdrawal of cigars, cigarettes, or cigarette papers or tubes subject to internal revenue tax, the statement... will be finally due upon liquidation. (e) Permit for release of merchandise. When the duties and other...

  18. 19 CFR 144.38 - Withdrawal for consumption.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... provided in § 141.61(e) of this chapter. (b) Withdrawal for exportation to Canada or Mexico. A withdrawal... withdrawal of cigars, cigarettes, or cigarette papers or tubes subject to internal revenue tax, the statement... will be finally due upon liquidation. (e) Permit for release of merchandise. When the duties and other...

  19. 19 CFR 144.38 - Withdrawal for consumption.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... provided in § 141.61(e) of this chapter. (b) Withdrawal for exportation to Canada or Mexico. A withdrawal... withdrawal of cigars, cigarettes, or cigarette papers or tubes subject to internal revenue tax, the statement... will be finally due upon liquidation. (e) Permit for release of merchandise. When the duties and other...

  20. 5 CFR 1650.31 - Age-based withdrawals.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Age-based withdrawals. 1650.31 Section... FUNDS FROM THE THRIFT SAVINGS PLAN In-Service Withdrawals § 1650.31 Age-based withdrawals. (a) A participant who has reached age 591/2 and who has not separated from Government employment is eligible to...