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

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.

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 ...

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.

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.

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...

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.

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...

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.

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

[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.

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.

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...

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

[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

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.

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

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.

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 ...

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

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.

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

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.

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.

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

SSRI and SNRI withdrawal symptoms reported on an internet forum.

PubMed

Stockmann, Tom; Odegbaro, Dolapo; Timimi, Sami; Moncrieff, Joanna

2018-05-09

Antidepressant withdrawal symptoms are well-recognised, but their potential duration remains uncertain. We aimed to describe the characteristics of withdrawal associated with two popular classes of antidepressants, including duration. We analysed the content of a sample of posts on an antidepressant withdrawal website. We compared the characteristics of withdrawal associated with SSRIs and SNRIs, including time of onset, duration and nature of symptoms. 110 posts about SSRI withdrawal, and 63 concerning SNRI withdrawal, were analysed. The mean duration of withdrawal symptoms was significantly longer with SSRIs than SNRIs: 90.5 weeks (standard deviation, SD, 150.0) and 50.8 weeks (SD 76.0) respectively; p = 0.043). Neurological symptoms, such as 'brain zaps,' were more common among SNRI users (p = 0.023). Psychosexual/genitourinary symptoms may be more common among SSRI users (p = 0.054). The website aims to help people with antidepressant withdrawal, and is therefore likely to attract people who have difficulties. Length of prior use of antidepressants was long, with a mean of 252.2 weeks (SD 250.8). People accessing antidepressant withdrawal websites report experiencing protracted withdrawal symptoms. There are some differences in the characteristics of withdrawal associated with different classes of antidepressants.

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

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

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.

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

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

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).

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.

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.

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.

Withdrawal symptoms in internet gaming disorder: A systematic review.

PubMed

Kaptsis, Dean; King, Daniel L; Delfabbro, Paul H; Gradisar, Michael

2016-02-01

Internet gaming disorder (IGD) is currently positioned in the appendix of the DSM-5 as a condition requiring further study. The aim of this review was to examine the state of current knowledge of gaming withdrawal symptomatology, given the importance of withdrawal in positioning the disorder as a behavioral addiction. A total of 34 studies, including 10 qualitative studies, 17 research reports on psychometric instruments, and 7 treatment studies, were evaluated. The results indicated that the available evidence on Internet gaming withdrawal is very underdeveloped. Internet gaming withdrawal is most consistently referred to as 'irritability' and 'restlessness' following cessation of the activity. There exists a concerning paucity of qualitative studies that provide detailed clinical descriptions of symptoms arising from cessation of internet gaming. This has arguably compromised efforts to quantify withdrawal symptoms in empirical studies of gaming populations. Treatment studies have not reported on the natural course of withdrawal and/or withdrawal symptom trajectory following intervention. It is concluded that many more qualitative clinical studies are needed, and should be prioritised, to develop our understanding of gaming withdrawal. This should improve clinical descriptions of problematic internet gaming and in turn improve the quantification of IGD withdrawal and thus treatments for harmful internet gaming. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

implemented this criterion recorded an improvement to 100% compliance. None of the patients in the pilot were transferred to the intensive care unit (ICU) for reasons relating to alcohol withdrawal. The outcomes of this project demonstrated alcohol withdrawal management can be safely undertaken outside the ICU when the patients are appropriately assessed and treated for the severity of their withdrawal symptoms. This new clinical program significantly impacted on continuity of care. Challenges were resolved using an interdisciplinary team approach. The project resulted in plans for further areas of work concerning alcohol withdrawal management, including adoption of similar approaches by other acute and transitional care units. The Joanna Briggs Institute.

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

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

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.

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

Youth Withdrawal Moderates the Relationhips between Neighborhood Factors and Internalizing Symptoms in Adolescence

PubMed Central

Rabinowitz, Jill A.; Drabick, Deborah A.G.; Reynolds, Maureen D.

2015-01-01

Adolescents higher in temperamental withdrawal are at risk for anxiety and depressive symptoms; however, not all youth higher in withdrawal exhibit internalizing symptoms, suggesting that contextual factors may influence these relationships. We examined whether youth withdrawal moderates the relationships between neighborhood processes (crime, social cohesion) and internalizing symptoms and whether findings were consistent with diathesis-stress or differential susceptibility hypotheses. Participants were 775 adolescents (M=15.50 ± 0.56 years, 72% male, 76% White). Adolescents higher in withdrawal manifested higher internalizing symptoms in the context of lower neighborhood crime and lower neighborhood social cohesion than youth lower in withdrawal, supporting diathesis-stress. These findings elucidate neighborhood processes associated with internalizing symptoms, which can inform models of risk and resilience for these symptoms among children who differ in temperamental withdrawal. PMID:26149949

Anhedonia and anxiety sensitivity: prospective relationships to nicotine withdrawal symptoms during smoking cessation.

PubMed

Langdon, Kirsten J; Leventhal, Adam M; Stewart, Sherry; Rosenfield, David; Steeves, Dan; Zvolensky, Michael J

2013-05-01

The aim of the present investigation was to explore the main and interactive effects of anhedonic depressive symptoms and anxiety sensitivity in terms of the individual components of nicotine withdrawal symptoms experienced on quit day as well as throughout the initial 14 days of cessation. Participants included 65 daily cigarette smokers (38 women; Mage = 46.08 years, SD = 9.12) undergoing psychosocial-pharmacological cessation treatment. Results indicated that, after controlling for the effects of participant sex and nicotine dependence, anhedonic depression symptoms, but not anxiety sensitivity, significantly predicted quit day levels of mood-based nicotine withdrawal symptoms. Conversely, anxiety sensitivity, but not anhedonic depression symptoms, was significantly related to the change in most nicotine withdrawal symptoms over time. Finally, our results revealed a significant interaction between anxiety sensitivity and anhedonic depression symptoms related to the slope of certain withdrawal symptoms over time. Specifically, among participants with higher levels of anxiety sensitivity, greater levels of anhedonic depression symptoms were related to greater increases in withdrawal symptoms over time for two of the nine anxiety-relevant components of nicotine withdrawal (restlessness and frustration). Among high anxiety-sensitivity persons, compared with those low in anxiety sensitivity, anhedonic depression symptoms may be more relevant to the experience of some withdrawal symptoms being more intense and persistent during the early phases of quitting.

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

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.

[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.

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.

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.

Tobacco withdrawal symptoms mediate motivation to reinstate smoking during abstinence.

PubMed

Aguirre, Claudia G; Madrid, Jillian; Leventhal, Adam M

2015-08-01

Withdrawal-based theories of addiction hypothesize that motivation to reinstate drug use following acute abstinence is mediated by withdrawal symptoms. Experimental tests of this hypothesis in the tobacco literature are scant and may be subject to methodological limitations. This study utilized a robust within-subject laboratory experimental design to investigate the extent to which composite tobacco withdrawal symptomatology level and 3 unique withdrawal components (i.e., low positive affect, negative affect, and urge to smoke) mediated the effect of smoking abstinence on motivation to reinstate smoking. Smokers (≥10 cigarettes per day; N = 286) attended 2 counterbalanced sessions at which abstinence duration was differentially manipulated (1 hr vs. 17 hr). At both sessions, participants reported current withdrawal symptoms and subsequently completed a task in which they were monetarily rewarded proportional to the length of time they delayed initiating smoking, with shorter latency reflecting stronger motivation to reinstate smoking. Abstinence reduced latency to smoking initiation and positive affect and increased composite withdrawal symptom level, urge, and negative affect. Abstinence-induced reductions in latency to initiating smoking were mediated by each withdrawal component, with stronger effects operating through urge. Combined analyses suggested that urge, negative affect, and low positive affect operate through empirically unique mediational pathways. Secondary analyses suggested similar effects on smoking quantity, few differences among specific urge and affect subtypes, and that dependence amplifies some abstinence effects. This study provides the first experimental evidence that within-person variation in abstinence impacts motivation to reinstate drug use through withdrawal. Urge, negative affect, and low positive affect may reflect unique withdrawal-mediated mechanisms underlying tobacco addiction. (c) 2015 APA, all rights reserved).

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

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.

[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.

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.

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

The effects of e-cigarette visual appearance on craving and withdrawal symptoms in abstinent smokers.

PubMed

Dawkins, Lynne; Munafò, Marcus; Christoforou, Gina; Olumegbon, Naomi; Soar, Kirstie

2016-02-01

Electronic cigarette (e-cigarette) use is becoming increasing popular among smokers, and there is a plethora of devices available. Nicotine delivery is clearly important for reducing tobacco craving and withdrawal symptoms, but other sensorimotor aspects of e-cigarettes (such as visual appearance) may contribute to this effect. This study explored whether it is important for an e-cigarette to visually resemble a tobacco cigarette in order to reduce craving and withdrawal symptoms. Sixty-three cigarette smokers (40% female, aged 18-65 years) who were not current e-cigarette users were randomly allocated to take ten 3-s puffs from either a white or a red first-generation e-cigarette following overnight abstinence. Current craving (urge to smoke) and nicotine withdrawal symptoms (using the Mood and Physical Symptoms Scale [MPSS]) were measured before and 10 min after use. Linear regression revealed higher craving and withdrawal symptoms in the red condition versus the white condition, but only among those who were e-cigarette naive (craving: B = .76, p = .009; withdrawal symptoms: B = 2.18, p = .009), not among those with e-cigarette experience (craving: B = -.08, p = .89; withdrawal symptoms: B = .24, p = .81), and these effects differed between groups (p = .04 and 0.01 for craving and withdrawal symptoms, respectively). In conclusion, cigarette-like appearance was associated with lower craving and withdrawal symptoms, but only for those with no prior e-cigarette experience. This effect, putatively mediated via classical conditioning or expectancies, may aid understanding of smokers' initial preferences for "cigalike" e-cigarette devices. (c) 2016 APA, all rights reserved).

Psychological and Pharmacological Influences in Cigarette Smoking Withdrawal: Effects of Nicotine Gum and Expectancy on Smoking Withdrawal Symptoms and Relapse.

ERIC Educational Resources Information Center

Gottlieb, Andrew M.; And Others

1987-01-01

Examined effects of expectancy and nicotine depletion on withdrawal symptoms by giving 109 smokers nicotine gum or placebo. Subjects who believed they had nicotine gum reported fewer physical symptoms of withdrawal, showed less arousal, and smoked fewer cigarettes than did those who thought they had placebo. Actual nicotine content of gum had no…

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.

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

Effect of thought suppression on desire to smoke and tobacco withdrawal symptoms.

PubMed

Erskine, James A K; Ussher, Michael; Cropley, Mark; Elgindi, Abdelaziz; Zaman, Manzir; Corlett, Bethan

2012-01-01

Suppressing smoking thoughts has been shown to result in elevated smoking. However, the effect of suppressing smoking thoughts on desire to smoke and withdrawal symptoms has not been investigated. We examined the effects of suppressing smoking thoughts on the subsequent desire to smoke and on tobacco withdrawal symptoms, relative to groups that were either thinking about anything they wished or actively thinking about smoking. A randomised experimental study compared the effects of three manipulations (suppressed smoking thoughts, expressed smoking thoughts and thoughts of anything they wished) on desire and withdrawal immediately after the manipulation and 5 and 10 min after. Suppressing smoking thoughts did not result in elevated subsequent desire to smoke, relative to the other manipulations. Suppressing smoking thoughts resulted in a significant elevation in hunger ratings, relative to the other manipulations, at all measurement times. There were no significant effects for the other withdrawal symptoms. Self-reported greater use of thought suppression in everyday life was significantly associated with greater desire to smoke at baseline and was associated with lower mindfulness scores. Laboratory-instructed suppression of smoking thoughts is associated with increased reports of hunger but did not lead to increases in other withdrawal symptoms or elevated desire to smoke. Reports of everyday use of thought suppression are associated with elevated desire to smoke at baseline. Further investigations need to assess the effect of suppressing smoking cravings, instead of general smoking thoughts, on desire to smoke and tobacco withdrawal.

Effect of Stress and Bupropion on Craving, Withdrawal Symptoms, and Mood in Smokers

PubMed Central

Drone, David; Thuras, Paul; Hatsukami, Dorothy K.; Brauer, Lisa; Adson, David E.; al’Absi, Mustafa

2011-01-01

Introduction: Studies suggest that in smokers attempting to quit smoking, the occurrence of stressful events is associated with smoking relapse. The purpose of this study was to determine the effect of bupropion (an agent known to increase smoking cessation rates) on the craving, withdrawal, and mood response to stressful tasks administered in a laboratory setting. Methods: Response to three tasks (a speech, math, and cold pressor task) was measured in 65 smokers during ad libitum smoking. Smokers were then randomized to either bupropion or placebo. Fourteen days after starting medication, 43 subjects (28 receiving bupropion and 15 receiving placebo) quit smoking and laboratory procedures were repeated on the third day of abstinence. Results: Prior to cessation, stressors presented in a laboratory setting increased craving, nicotine withdrawal symptoms, and subjective distress but decreased positive affect. Thirty minutes of relaxation after the stressors did not result in these measures returning to prestress levels. During the nicotine withdrawal period, stress-induced responses were generally smaller than during the precessation period. Bupropion (relative to placebo) reduced overall levels of craving and withdrawal symptoms but did not have significant effects on response to stress during the nicotine withdrawal period. Conclusions: This study demonstrates that stress results in sustained increases in craving and withdrawal symptoms and changes in mood symptoms and that bupropion affects overall levels of these symptoms. Further research is needed to determine if modifying response to stress is predictive of an effective treatment for facilitating smoking cessation. PMID:21378081

Short-course diphenoxylate hydrochloride for treatment of methadone withdrawal symptoms.

PubMed

Ives, T J; Stults, C C

1983-11-01

The authors conducted a preliminary trial of a 5-day course of diphenoxylate in the treatment of out-patients with methadone withdrawal symptoms. Diphenoxylate provided substantial relief from detoxification symptoms with no drug-associated adverse effects.

Trajectories of abstinence-induced Internet gaming withdrawal symptoms: A prospective pilot study.

PubMed

Kaptsis, Dean; King, Daniel L; Delfabbro, Paul H; Gradisar, Michael

2016-12-01

Internet Gaming Disorder (IGD) is positioned in the appendix of the DSM-5 as a condition requiring further study. The IGD criteria refer to withdrawal symptoms, including irritability, anxiety, or sadness, that follow cessation of Internet gaming (APA, 2013). The aim of this study was to prospectively examine the nature of Internet gaming withdrawal symptoms, if they occur, under gaming abstinence conditions. This study employed a repeated-measures protocol to examine the cognitive-affective reactions of participants undertaking an 84-h Internet gaming abstinence period. The sample included individuals who met the IGD criteria as well as those who regularly played Internet games but did not meet the IGD criteria. Outcome variables included affect (positive and negative), psychological distress (depression, anxiety, stress), and Internet gaming withdrawal symptoms (craving/urge, thoughts about gaming, inability to resist gaming). A total of 24 participants ( M age  = 24.6 years, SD  = 5.8) were recruited from online gaming communities, and completed a series of online surveys before, during, and after abstaining from Massively Multiplayer Online (MMO) games. Both the IGD group and the non-IGD group experienced an abstinence-induced decline in withdrawal symptomatology, negative affect, and psychological distress. The IGD group experienced its largest decline in withdrawal symptomatology within the first 24 h of abstinence. These preliminary data suggest that gaming withdrawal symptoms may follow, at least initially, negative linear and quadratic trends. Further prospective work in larger samples involving longer periods of abstinence is required to verify and expand upon these observations.

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.

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.

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.

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.

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

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.

Opioid interruptions, pain, and withdrawal symptoms in nursing home residents.

PubMed

Redding, Sarah E; Liu, Sophia; Hung, William W; Boockvar, Kenneth S

2014-11-01

Interruptions in opioid use have the potential to cause pain relapse and withdrawal symptoms. The objectives of this study were to observe patterns of opioid interruption during acute illness in nursing home residents and examine associations between interruptions and pain and withdrawal symptoms. Patients from 3 nursing homes in a metropolitan area who were prescribed opioids were assessed for symptoms of pain and withdrawal by researchers blinded to opioid dosage received, using the Brief Pain Inventory Scale and the Clinical Opioid Withdrawal Scale, respectively, during prespecified time periods. The prespecified time periods were 2 weeks after onset of acute illness (eg, urinary tract infection), and 2 weeks after hospital admission and nursing home readmission, if they occurred. Opioid dosing was recorded and a significant interruption was defined as a complete discontinuation or a reduction in dose of >50% for ≥1 day. The covariates age, sex, race, comorbid conditions, initial opioid dose, and initial pain level were recorded. Symptoms pre- and post-opioid interruptions were compared and contrasted with those in a group without opioid interruptions. Sixty-six patients receiving opioids were followed for a mean of 10.9 months and experienced a total of 104 acute illnesses. During 64 (62%) illnesses, patients experienced any reduction in opioid dosing, with a mean (SD) dose reduction of 63.9% (29.9%). During 39 (38%) illnesses, patients experienced a significant opioid interruption. In a multivariable model, residence at 1 of the 3 nursing homes was associated with a lower risk of interruption (odds ratio = 0.073; 95% CI, 0.009 to 0.597; P < 0.015). In patients with interruptions, there were statistically insignificant changes in mean (SD) pain score (difference -0.50 [2.66]; 95% CI, -3.16 to 2.16) and withdrawal score (difference -0.91 [3.12]; 95% CI, -4.03 to 2.21) after the interruption as compared with before interruption. However, when compared with

[Preventive withdrawal from work, psychosocial work demands and major depressive symptoms].

PubMed

Fall, A; Goulet, L; Vézina, M

2015-12-01

Our study objectives were as follows: assess exposure to psychosocial work demands among working pregnant women and women on preventive withdrawal from work; and measure the association between psychosocial work demands and major depressive symptoms, according to time of withdrawal from work. Karasek's abbreviated scale was used to measure psychosocial work demands (Job strain and "Iso-strain") and CES-D scale (Center for Epidemiological Studies Depression Scale) was used to measure major depressive symptoms (CES-D score≥23), at 24-26 weeks of pregnancy, among 3043 pregnant women in Montreal (Quebec) who worked at paid jobs at least 15 h/week and at least four consecutive weeks since the beginning of their pregnancy. Multivariate logistic regression models were built. At 24-26 weeks of pregnancy, 31.4% (956/3043) of pregnant women were on preventive withdrawal from work. They were more in "high-strain" (31.1% vs. 21.1%) and "Iso-strain" groups (21.0% vs. 14.2%) than those who continued to work (P<0.0001). The prevalence of major depressive symptoms was higher in women on preventive withdrawal from work (10.8%; CI 95%: 8.9 to 12.9) compared to working women (7.1%; CI 95%: 6.1-8.3). After adjustment for personal and professional risk factors, "Iso-strain" remained significantly associated with major depressive symptoms in working women (adjusted OR=1.75; CI 95%: [1.05 to 2.92]) and women on preventive withdrawal from work, regardless of duration of activity before withdrawal: 4 to 12 weeks (adjusted OR=2.72; CI 95%: [1.19-6.12]), 13 to 20 weeks (adjusted OR=3.51; CI 95%: [1.54-7.97]), and ≥21 weeks (adjusted OR=2.39; CI 95%: [1.10-5.20]). Psychosocial work demands are an important risk factor for the mental health of pregnant workers and require that preventive actions be put forward. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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.

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.

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.

Caffeine withdrawal symptoms and self-administration following caffeine deprivation.

PubMed

Mitchell, S H; de Wit, H; Zacny, J P

1995-08-01

This study examined the effects of complete or partial caffeine deprivation on withdrawal symptomatology and self-administration of coffee in caffeine-dependent coffee drinkers. Nine habitual coffee drinkers abstained from dietary sources of caffeine for 33.5 h. Caffeine deprivation was manipulated by administering capsules containing 0%, 50%, or 100% of each subject's daily caffeine intake (complete, partial, and no deprivation conditions). Caffeine withdrawal symptomatology was measured using self-report questionnaires. Caffeine self-administration was measured using: i) the amount of coffee subjects earned on a series of concurrent random-ratio schedules that yielded coffee and money reinforcers; ii) the amount of earned coffee they consumed. Saliva samples revealed that subjects complied with the caffeine abstinence instructions. Caffeine withdrawal symptoms occurred reliably following complete caffeine deprivation, though not in the partial deprivation condition. Caffeine self-administration was not related to deprivation condition. We conclude that caffeine withdrawal symptomatology is not necessarily associated with increased caffeine consumption.

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

Mothers' early depressive symptoms and children's first-grade adjustment: a transactional analysis of child withdrawal as a mediator.

PubMed

Yan, Ni; Dix, Theodore

2014-05-01

The depression-inhibition hypothesis suggests that mothers' depressive symptoms undermine development because they lead children to withdraw from social contact. To test this, this study examined whether poor first-grade adjustment among children of mothers with depressive symptoms is mediated by the emergence of child withdrawal in early development. Based on 1,364 dyads, four waves of data spanning from 24 months to first grade (7 years) were used to examine paths by which children's withdrawal mediates relations between mothers' early depressive symptoms and three first-grade outcomes: social competence, academic performance, and externalizing behavior problems. Structural equation modeling revealed three principal paths. First, direct relations were observed: Mothers' depressive symptoms predicted early child withdrawal and increases in child withdrawal over time, which predicted poor first-grade adjustment. Second, reciprocal relations were observed: Mothers' depressive symptoms predicted child withdrawal, which predicted increases in depressive symptoms. Third, relations via mother-child mutual responsiveness were observed: Depression-related increases in child withdrawal predicted declines in mutual responsiveness, which predicted poor first-grade adjustment. The findings suggest that, due to its interdependence with maternal depression and low mother-child mutual responsiveness over time, child withdrawal may play an important role in the poor first-grade adjustment of children whose mothers are high in depressive symptoms. © 2013 The Authors. Journal of Child Psychology and Psychiatry. © 2013 Association for Child and Adolescent Mental Health.

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.

Preliminary effects of progressive muscle relaxation on cigarette craving and withdrawal symptoms in experienced smokers in acute cigarette abstinence: a randomized controlled trial.

PubMed

Limsanon, Thatsanee; Kalayasiri, Rasmon

2015-03-01

Cigarette craving usually occurs in conjunction with unpleasant feelings, including stress, as part of a withdrawal syndrome. Progressive muscle relaxation (PMR), a behavioral technique used to reduce stress by concentrating on achieving muscle relaxation, may reduce levels of cigarette craving and other substance-related negative feelings and withdrawal symptoms. Demographic and cigarette use data were collected from 32 experienced smokers at the King Chulalongkorn Memorial Hospital, Bangkok, Thailand using the Semi-Structured Assessment for Drug Dependence and Alcoholism. Participants were asked to refrain from smoking for at least 3 hours before the visit (acute abstinence) and were randomly allocated to a 1-session PMR group (n =16) or a control activity group (e.g., reading newspaper, n =16). The intervention group was instructed to practice PMR individually in a quiet, private, air-conditioned room for about 20minutes. Craving, other substance-related feelings, and autonomic nervous responses (e.g., blood pressure and pulse rate) were assessed immediately before and after the 1-session intervention. There were no differences in demographics, cigarette use/dependence, and baseline craving characteristics between the PMR and control groups. However, the control group had higher levels of high and paranoia feeling, and pulse rate than the PMR group at baseline. After practicing PMR, but not after a control activity, smokers undergoing acute abstinence had significantly lower levels of cigarette craving, withdrawal symptoms, and systolic blood pressure than at baseline. After controlling for baseline differences, abstaining smokers using PMR had lower levels of cigarette craving, withdrawal symptoms, and systolic blood pressure than smokers who undertook a control activity. PMR significantly reduces cigarette craving, withdrawal symptoms, and blood pressure in smokers undergoing acute abstinence. PMR may be used as an adjunct to cigarette dependency treatments

Acute exercise effects on smoking withdrawal symptoms and desire to smoke are not related to expectation.

PubMed

Daniel, James Z; Cropley, Mark; Fife-Schaw, Chris

2007-11-01

Recent research has shown that 10 min of moderate intensity exercise reduce smoking withdrawal symptoms and desire to smoke in acutely abstinent smokers. The aim of the current study was to determine whether the reductions are related to participant expectation of these effects. Forty-five sedentary participants who had smoked ten or more cigarettes per day for at least 3 years reported their expectation of the effects of exercise on smoking withdrawal symptoms. Approximately 1 month later, participants were randomly assigned to one of three groups after 11-15 h of overnight smoking abstinence. Each group read either a positive, negative or neutral statement concerning exercise effects on smoking withdrawal symptoms. They rated their expectation again and then completed 10 min of moderate intensity exercise on a stationary bicycle ergometer. Using standardised scales, participants rated smoking withdrawal symptoms and desire to smoke at 10, 5 and 0 min before exercise, then at 5 and 10 min during exercise and 15 and 20 min post-exercise. Expectation of exercise effects on withdrawal were manipulated in the predicted directions. No significant group main effects were found for any symptom. Significant reductions in symptoms and desire to smoke occurred during and after exercise regardless of participant expectation. Ten minutes of moderate intensity exercise can lead to reductions in desire to smoke and smoking withdrawal symptoms, which are not due to the participant's expectation of exercise effects. These findings support the use of short periods of exercise as an aid to smoking cessation.

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.

The comparative efficacy of first- versus second-generation electronic cigarettes in reducing symptoms of nicotine withdrawal.

PubMed

Lechner, William V; Meier, Ellen; Wiener, Josh L; Grant, DeMond M; Gilmore, Jenna; Judah, Matt R; Mills, Adam C; Wagener, Theodore L

2015-05-01

Currently, electronic cigarettes (e-cigarettes) are studied as though they are a homogeneous category. However, there are several noteworthy differences in the products that fall under this name, including potential differences in the efficacy of these products as smoking cessation aids. The current study examined the comparative efficacy of first- and second-generation e-cigarettes in reducing nicotine withdrawal symptoms in a sample of current smokers with little or no experience of using e-cigarettes. Twenty-two mildly to moderately nicotine-dependent individuals were randomized to a cross-over design in which they used first- and second-generation e-cigarettes on separate days with assessment of withdrawal symptoms directly prior to and after product use. A community-based sample recruited in the Midwest region of the United States reported a mean age of 28.6 [standard deviation (SD) = 12.9]. The majority were male (56.5%), Caucasian (91.3%), reported smoking an average of 15.2 (SD = 9.6) tobacco cigarettes per day, and a mean baseline carbon monoxide (CO) level of 18.7 parts per million (p.p.m.). Symptoms of withdrawal from nicotine were measured via the Mood and Physical Symptoms Scale. Analysis of changes in withdrawal symptoms revealed a significant time × product interaction F(1, 21)  = 5.057, P = 0.036, n(2) P  = 0.202. Participants experienced a larger reduction in symptoms of nicotine withdrawal after using second-generation compared with first-generation e-cigarettes. Second-generation e-cigarettes seem to be more effective in reducing symptoms of nicotine withdrawal than do first-generation e-cigarettes. © 2015 Society for the Study of Addiction.

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.

Harm reduction-a systematic review on effects of alcohol reduction on physical and mental symptoms.

PubMed

Charlet, Katrin; Heinz, Andreas

2017-09-01

Based on the knowledge that alcohol misuse causes a multitude of diseases and increased mortality, this systematic review examines whether a reduction of the individual alcohol consumption can contribute to a minimization of health risks within a harm reduction approach. In fact, the reviewed 63 studies indicate that interventions aiming at alcohol reduction (including total abstinence as one possible therapeutic aim) indeed resulted in or were associated with positive effects in harmful, hazardous or alcohol-dependent drinkers. Major benefits were observed for reducing alcohol-associated injuries, recovery of ventricular heart function in alcoholic cardiomyopathy, blood pressure lowering, normalization of biochemical parameter, body weight reduction, histological improvement in pre-cirrhotic alcohol-related liver disease and slowed progression of an already existing alcohol-attributable liver fibrosis. Furthermore, reduced withdrawal symptoms, prevalence of psychiatric episodes and duration of in-patient hospital days, improvement of anxiety and depression symptoms, self-confidence, physical and mental quality of life, fewer alcohol-related adverse consequences as well as lower psychosocial stress levels and better social functioning can result from reduced alcohol intake. The reviewed literature demonstrated remarkable socioeconomic cost benefits in areas such as the medical health-care system or workforce productivity. Individuals with heightened vulnerability further benefit significantly from alcohol reduction (e.g. hypertension, hepatitis C, psychiatric co-morbidities, pregnancy, but also among adolescents and young adults). Concluding, the reviewed studies strongly support and emphasize the importance and benefits of early initial screening for problematic alcohol use followed by brief and other interventions in first contact medical health-care facilities to reduce alcohol intake. © 2016 Society for the Study of Addiction.

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.

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.

Drug withdrawal symptoms in children after continuous infusions of fentanyl.

PubMed

French, J P; Nocera, M

1994-04-01

The purpose of this research was to determine the extent to which critically ill infants exhibited signs and symptoms of narcotic withdrawal after receiving continuous infusions of fentanyl. The convenience sample consisted of 12 pediatric intensive care unit (PICU) patients under 25 months of age who received fentanyl infusions for at least 24 hours. Drug withdrawal symptoms were monitored using the Neonatal Abstinence Score Tool (NAST), which assigns a score to each behavior indicative of withdrawal. A score of 8 or greater indicates Neonatal Abstinence Syndrome (NAS). Scoring began 4 hours after discontinuation of fentanyl and was conducted once per hour for 8 hours. Six subjects had a NAST score exceeding 8; these infants frequently exhibited tremors with or without stimulation, increased muscle tone, insomnia, and increased respiratory rate and effort. There were significant correlations between fentanyl dosage and NAST score (r = .76, p < 0.01), between length of infusion of fentanyl and NAST score (r = .70, p < 0.05), and between chloral hydrate dosage and NAST score (r = .62, p < 0.05). These findings suggest the need for an observation protocol and a possible weaning regimen after fentanyl is discontinued.

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.

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

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.

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.

The role of distress intolerance for panic and nicotine withdrawal symptoms during a biological challenge.

PubMed

Farris, Samantha G; Zvolensky, Michael J; Otto, Michael W; Leyro, Teresa M

2015-07-01

Distress intolerance is linked to the maintenance of panic disorder and cigarette smoking, and may underlie both problems. Smokers (n = 54; 40.7% panic disorder) were recruited for an experimental study; half were randomly assigned to 12-hour nicotine deprivation and half smoked as usual. The current investigation consisted of secondary, exploratory analyses from this larger experimental study. Four distress intolerance indices were examined as predictors of anxious responding to an emotional elicitation task (10% carbon dioxide (CO2)-enriched air challenge); anxious responding was in turn examined as a predictor of post-challenge panic and nicotine withdrawal symptoms. The Distress Tolerance Scale (DTS) was significantly negatively associated with anxious responding to the challenge (β = -0.41, p = 0.017). The DTS was negatively associated with post-challenge increases nicotine withdrawal symptoms indirectly through the effect of anxious responding to the challenge (b = -0.485, CI95% (-1.095, -0.033)). This same indirect effect was found for post-challenge severity of panic symptoms (b = -0.515, CI95% (-0.888, -0.208)). The DTS was directly predictive of post-challenge increases nicotine withdrawal symptoms, in the opposite direction (β = 0.37, p = 0.009), but not panic symptom severity. Anxious responding in response to stressful experiences may explain the impact of perceived distress intolerance on panic and nicotine withdrawal symptom expression. © The Author(s) 2015.

Craving and Withdrawal Symptoms During Smoking Cessation: Comparison of Pregnant and Non-Pregnant Smokers.

PubMed

Berlin, Ivan; Singleton, Edward G; Heishman, Stephen J

2016-04-01

Although pregnant smokers are aware of the negative peri- and postnatal health consequences of smoking, the cessation rate in pregnancy is low, raising the question of why pregnant smokers have difficulty quitting. Reasons might be that pregnant smokers experience more intense craving and withdrawal symptoms than non-pregnant smokers. We compared craving and withdrawal in 306 pregnant smokers versus 93 non-pregnant women using data from two smoking cessation trials. Complete data were analyzed using pre-quit and post-quit (2 weeks after quit date) craving and withdrawal measured by the 12-item French Tobacco Craving Questionnaire (FTCQ-12) and French Minnesota Nicotine Withdrawal Scale (FMNWS). Pregnant smokers started smoking and smoked regularly earlier and succeeded far less at quitting smoking by week 2 than the general population of smokers (11% versus 43%). Post-quit date FTCQ-12 general score was higher in pregnant smokers compared to comparison groups, and was driven by elevated emotionality and expectancy. FMNWS decreased significantly less among pregnant smokers than among non-pregnant smokers. Insufficient reduction of craving and withdrawal symptoms in response to a quit attempt may partially explain why pregnant smokers may have more difficulty quitting than non-pregnant smokers. Because this was a historical comparison, findings are preliminary; however, they might foster further investigation of differences in craving and withdrawal symptoms in pregnant versus non-pregnant smokers. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

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

Blockade of Endocannabinoid Hydrolytic Enzymes Attenuates Precipitated Opioid Withdrawal Symptoms in MiceS⃞

PubMed Central

Ramesh, Divya; Ross, Gracious R.; Schlosburg, Joel E.; Owens, Robert A.; Abdullah, Rehab A.; Kinsey, Steven G.; Long, Jonathan Z.; Nomura, Daniel K.; Sim-Selley, Laura J.; Cravatt, Benjamin F.; Akbarali, Hamid I.

2011-01-01

Δ9-Tetrahydrocannbinol (THC), the primary active constituent of Cannabis sativa, has long been known to reduce opioid withdrawal symptoms. Although THC produces most of its pharmacological actions through the activation of CB1 and CB2 cannabinoid receptors, the role these receptors play in reducing the variety of opioid withdrawal symptoms remains unknown. The endogenous cannabinoids, N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonylglycerol (2-AG), activate both cannabinoid receptors but are rapidly metabolized by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. The objective of this study was to test whether increasing AEA or 2-AG, via inhibition of their respective hydrolytic enzymes, reduces naloxone-precipitated morphine withdrawal symptoms in in vivo and in vitro models of opioid dependence. Morphine-dependent mice challenged with naloxone reliably displayed a profound withdrawal syndrome, consisting of jumping, paw tremors, diarrhea, and weight loss. THC and the MAGL inhibitor 4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate (JZL184) dose dependently reduced the intensity of most measures through the activation of CB1 receptors. JZL184 also attenuated spontaneous withdrawal signs in morphine-dependent mice. The FAAH inhibitor N-(pyridin-3-yl)-4-(3-(5-(trifluoromethyl)pyridin-2-yloxy)benzyl)-piperdine-1-carboxamide (PF-3845) reduced the intensity of naloxone-precipitated jumps and paw flutters through the activation of CB1 receptors but did not ameliorate incidence of diarrhea or weight loss. In the final series of experiments, we investigated whether JZL184 or PF-3845 would attenuate naloxone-precipitated contractions in morphine-dependent ilea. Both enzyme inhibitors attenuated the intensity of naloxone-induced contractions, although this model does not account mechanistically for the autonomic withdrawal responses (i.e., diarrhea) observed in vivo. These results indicate

Early adolescent symptoms of social phobia prospectively predict alcohol use.

PubMed

Dahne, Jennifer; Banducci, Anne N; Kurdziel, Gretchen; MacPherson, Laura

2014-11-01

The current study examined whether social phobia (SP) symptoms in early adolescence prospectively predicted alcohol use through middle adolescence in a community sample of youth. Data from an ongoing longitudinal study (N = 277) of mechanisms of HIV-related risk behaviors in youth were used to assess the extent to which SP symptoms in early adolescence (mean [SD] age = 11.00 years [0.81]) would predict alcohol use across five annual assessment waves. Adolescents completed measures of SP symptoms, depressive symptoms, and alcohol use at each wave. Higher SP symptoms at baseline predicted higher average odds of alcohol consumption during subsequent waves but did not significantly predict an increase in the odds of alcohol use as a function of time. Within a lagged model, SP symptoms measured at a prior assessment point (1 year earlier) predicted greater odds of drinking alcohol at the following assessment point. Importantly, alcohol use did not significantly predict SP symptoms over time. These results suggest that early SP symptoms are an important risk factor for increased odds of subsequent alcohol use. The present findings highlight that elevated SP symptoms place adolescents at risk for early alcohol use. Early interventions targeting SP symptoms may be crucial for the prevention of problematic alcohol use in early to mid-adolescence. Implications for prevention and treatment approaches are discussed.

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.

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

The relation between Bulimic symptoms and the social withdrawal syndrome during early adolescence.

PubMed

Rotenberg, Ken J; Sangha, Rajvir

2015-12-01

The short-term longitudinal study tested the hypothesis that there was a prospective relation between the social withdrawal syndrome and Bulimic symptoms during early adolescence. Ninety-six adolescents (47 males, mean age=13 years - 10 months) completed standardized scales assessing Bulimic symptoms, trust beliefs in others and loneliness at Time 1/T1 and again 5 months later at Time 2/T2. Analyses showed that: (1) Bulimic symptoms were negatively correlated with trust beliefs, (2) Bulimic symptoms were positively correlated with loneliness, and (3) trust beliefs were negatively correlated with loneliness. The SEM and mediation analyses showed that trust beliefs at T1 were negatively and concurrently associated with Bulimic symptoms at T1 and longitudinally (and negatively) predicted changes in Bulimic symptoms. It was found that loneliness at T1 statistically mediated those concurrent and longitudinal relations. The findings yielded support for the conclusion that the social withdrawal syndrome, as assessed by low trust beliefs and resulting experiences of loneliness, contributes to Bulimia nervosa during early adolescence. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Cannabis dependence in the San Francisco Family Study: age of onset of use, DSM-IV symptoms, withdrawal, and heritability

PubMed Central

Ehlers, Cindy L.; Gizer, Ian R.; Vieten, Cassandra; Gilder, David A.; Stouffer, Gina M.; Lau, Philip; Wilhelmsen, Kirk C.

2009-01-01

Cannabis is the most widely used illicit drug in the United States, yet the role of genetics in individual symptoms associated with cannabis use disorders has not been evaluated. The purpose of the present set of analyses was to describe the symptomatology and estimate the heritability of DSM-IV criteria/symptoms of cannabis dependence in a large sample of families. Participants were 2524 adults, participating in the University of California San Francisco (UCSF) Family Study of alcoholism. Seventy percent of the sample had ever used cannabis and 13.9% met DSM-IV criteria for cannabis dependence. Younger age at first cannabis use was found to be significantly associated with a shortened survival to becoming cannabis dependent. Although a greater percentage of men met criteria for cannabis dependence, women were found to demonstrate “telescoping” as indexed by a shorter survival time from initial use to dependence as compared to men. A cannabis withdrawal syndrome was identified in users, the primary symptoms of which were nervousness, appetite change, and sleep disturbance. Cannabis use (h2 = 0.31) and dependence (h2 = 0.20), age at first use, individual DSM-IV criteria for dependence, and cannabis-use associated symptoms of depression, trouble concentrating and paranoia were all found to be heritable. These findings suggest that within this population that cannabis use and dependence, as well as individual cannabis dependence symptoms have a significant heritable component, that cannabis dependence is more likely to occur when use begins during adolescence, and that the cannabis dependence syndrome includes a number of heritable untoward psychiatric side effects including withdrawal. PMID:19818563

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

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

The electronic-cigarette: effects on desire to smoke, withdrawal symptoms and cognition.

PubMed

Dawkins, Lynne; Turner, John; Hasna, Surrayyah; Soar, Kirstie

2012-08-01

Electronic cigarettes (e-cigarettes) are battery operated devices that deliver nicotine via inhaled vapour. Few studies have evaluated acute effects on craving and mood, and none have explored effects on cognition. This study aimed to explore the effects of the White Super e-cigarette on desire to smoke, nicotine withdrawal symptoms, attention and working memory. Eighty-six smokers were randomly allocated to either: 18 mg nicotine e-cigarette (nicotine), 0mg e-cigarette (placebo), or just hold the e-cigarette (just hold) conditions. Participants rated their desire to smoke and withdrawal symptoms at baseline (T1), and five (T2) and twenty (T3) minutes after using the e-cigarette ad libitum for 5 min. A subset of participants completed the Letter Cancellation and Brown-Peterson Working Memory Tasks. After 20 min, compared with the just hold group, desire to smoke and some aspects of nicotine withdrawal were significantly reduced in the nicotine and placebo group; the nicotine e-cigarette was superior to placebo in males but not in females. The nicotine e-cigarette also improved working memory performance compared with placebo at the longer interference intervals. There was no effect of nicotine on Letter Cancellation performance. To conclude, the White Super e-cigarette alleviated desire to smoke and withdrawal symptoms 20 min after use although the nicotine content was more important for males. This study also demonstrated for the first time that the nicotine e-cigarette can enhance working memory performance. Further evaluation of the cognitive effects of the e-cigarette and its efficacy as a cessation tool is merited. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

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

Bulimic symptoms and the social withdrawal syndrome.

PubMed

Rotenberg, Ken J; Bharathi, Carla; Davies, Helen; Finch, Tom

2013-08-01

One hundred and thirty-seven undergraduates (81 females; mean age = 21 years-10 months) completed the Bulimic SEDS subscale and standardized measures of trust beliefs in close others (mother, father, and friend), disclosure to them, and loneliness. Structural Equation Modelling yielded: (1) a negative path between Bulimic Symptoms and trust beliefs, (2) a positive path between trust beliefs and disclosure, (3) a negative path between trust beliefs and loneliness, and (4) a negative path between disclosure and loneliness. As expected, trust beliefs statistically mediated the relations between Bulimic Symptoms and both disclosure and loneliness and disclosure statistically mediated the relation between trust beliefs and loneliness. The findings supported the conclusion that individuals with bulimia nervosa are prone to the social withdrawal syndrome comprising a coherent and integrated pattern of low trust beliefs in close others, low disclosure to close others, and high loneliness. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

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

An Unreported Cause of Intrathecal Baclofen Withdrawal Symptoms in a Woman With Spastic Cerebral Palsy Who Received Intrathecal Gablofen.

PubMed

Duraski, Sylvia A; Sayyad, Anjum

2018-04-01

This article details an unreported potential cause of withdrawal symptoms in a patient with cerebral palsy who experienced intrathecal baclofen withdrawal shortly after placement of a baclofen pump with subsequent refill with Gablofen. Initial implantation of the baclofen pump with Lioresal occurred after a successful hospital trial of intrathecal injection via lumbar puncture. However, later, the patient did experience signs and symptoms of baclofen withdrawal after a pump refill was performed with Gablofen.

Prevalence, withdrawal symptoms and associated factors of khat chewing among students at Jimma University in Ethiopia.

PubMed

Abdeta, Tilahun; Tolessa, Daniel; Adorjan, Kristina; Abera, Mubarek

2017-04-17

Recently, khat chewing has become a common practice among high school, college, and university students. Regular khat chewing is thought to be a predisposing factor for different physical and mental health problems. It can lead to absenteeism from work and classes. In Ethiopia, to our knowledge no published study has investigated khat withdrawal symptoms. Therefore, this study was conducted to determine the prevalence, withdrawal symptoms, and associated factors of khat chewing among regular undergraduate students on the main campus of Jimma University in Ethiopia. The institution-based, cross-sectional study was conducted in January 2016. Data were collected from 651 main campus regular undergraduate students with a structured, self-administered questionnaire, entered into Epidata 3.1 and exported to SPSS version 20 for Windows. Bivariate and multivariate logistic regressions were used to explore associations and identify variables independently associated with khat chewing. The study found that the lifetime and current prevalence of khat chewing among students were 26.3% (95% CI: 24.3, 28.3) and 23.9% (95% CI: 21.94, 25.86), respectively. About 25.7% of students started chewing after joining university, and 60.5% of these students started during their first year. The main reason given for starting khat chewing was for study purposes (54.6%), followed by socialization purposes (42.3%). Among current khat chewers, 72.9% reported that they had chewed khat for 1 year or more and 68.2% reported that they had experienced various withdrawal symptoms. The most frequently reported withdrawal symptoms were feeling depressed, craving, and feeling fatigued. Being male, attending a place of worship daily/2-3 times per week, cannabis use, smoking cigarettes, and having family members currently chewing khat were independently associated with khat chewing. This study found that large numbers of university students were currently chewing khat. In this study withdrawal symptoms

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.

Shared familial risk between bulimic symptoms and alcohol involvement during adolescence.

PubMed

Baker, Jessica H; Munn-Chernoff, Melissa A; Lichtenstein, Paul; Larsson, Henrik; Maes, Hermine; Kendler, Kenneth S

2017-07-01

Twin studies show the established relation between bulimic symptoms and problematic alcohol involvement in adult females is partly due to shared familial factors, specifically shared genetic effects. However, it is unclear if similar shared etiological factors exist during adolescence or in males. We examined the familial overlap (i.e., genetic and common environmental correlations) between bulimic symptoms and various levels of alcohol involvement in 16- to 17-year-old female and male same-sex twin pairs using sex-specific biometrical twin modeling. Bulimic symptoms were assessed with the Eating Disorder Inventory-2. Alcohol involvement included alcohol use in the last month, having ever been intoxicated, and alcohol intoxication frequency. Results revealed 3 distinct patterns. First, in general, phenotypic correlations indicated statistically similar associations between bulimic symptoms and alcohol involvement in girls and boys. Second, common environmental overlap was significant for the bivariate associations including having ever been intoxicated. Third, moderate genetic correlations were observed between all bulimic symptoms and alcohol involvement in girls and moderate common environmental correlations were observed in boys for the more risky/deviant levels of involvement. Similar to adults, there is familial overlap between bulimic symptoms and alcohol involvement in adolescent girls and boys. These results could inform symptom- and sex-specific, developmentally targeted prevention and intervention programs for the comorbidity between bulimic symptoms and alcohol involvement. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Effect of fetal alcohol exposure on adult symptoms of nicotine, alcohol, and drug dependence.

PubMed

Yates, W R; Cadoret, R J; Troughton, E P; Stewart, M; Giunta, T S

1998-06-01

The objective of this study is to examine the effect of fetal alcohol exposure on later substance dependence using an adoption study method. One hundred ninety-seven adoptees were interviewed for substance abuse disorders, including nicotine, alcohol, and drug dependence. Twenty-one adoptees had mothers who drank during pregnancy. Adoptees with fetal alcohol exposure were compared with those without fetal alcohol exposure for symptoms of adult nicotine, alcohol, and drug dependence. Adoptee symptom counts for alcohol, drug, and nicotine dependence were higher for those exposed to alcohol in utero. The effect of fetal alcohol exposure remained after controlling for gender, biological parent alcohol dependence diagnosis, birth weight, gestational age and other environmental variables. Fetal alcohol exposure may produce increased risk for later nicotine, alcohol, and drug dependence. Possible effects of fetal alcohol exposure on development of adult substance use patterns needs attention in genetic studies of substance abuse.

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

Association between anxiety symptoms and problematic alcohol use in adolescents.

PubMed

Costa, Marianna de Abreu; Salum Junior, Giovanni Abrahão; Isolan, Luciano Rassier; Acosta, Jandira Rahmeier; Jarros, Rafaela Behs; Blaya, Carolina; Diemen, Lísia Von; Manfro, Gisele Gus

2013-01-01

Anxiety disorders are highly prevalent, affecting approximately 10% of individuals throughout life; its onset can be detected since early childhood or adolescence. Studies in adults have shown that anxiety disorders are associated with alcohol abuse, but few studies have investigated the association between anxiety symptoms and problematic alcohol use in early ages. To evaluate if anxiety symptoms are associated with problematic alcohol use in young subjects. A total of 239 individuals aged 10-17 years were randomly selected from schools located in the catchment area of Hospital de Clínicas de Porto Alegre. The Screen for Child Anxiety-Related Emotional Disorders (SCARED) was used to evaluate the presence of anxiety symptoms, and the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), to evaluate alcohol use. One hundred twenty-seven individuals (53.1% ) reported having already used alcohol. Of these, 14 individuals showed problematic alcohol use (5.8% ). There was no association between lifetime use of alcohol and anxiety symptoms, but mean SCARED scores in individuals with problematic alcohol use was higher if compared to those without problematic use, even after adjustment for age and gender (29.9±8.5 vs. 23.7±11.8, p < 0.001). Despite the limitation of a cross-sectional design, our study suggests that anxiety symptoms are associated with problematic alcohol use early in life.

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.

Alcohol craving and demand mediate the relation between posttraumatic stress symptoms and alcohol-related consequences.

PubMed

Tripp, Jessica C; Meshesha, Lidia Z; Teeters, Jenni B; Pickover, Alison M; McDevitt-Murphy, Meghan E; Murphy, James G

2015-10-01

Posttraumatic stress (PTS) symptoms are associated with alcohol-related consequences, but there is a need to understand mediators that may help explain the reasons for this relationship. Individuals with PTS may experience elevated craving and alcohol reward value (demand), which may contribute to risk for alcohol-related consequences. We examined relationships between PTS status, craving, alcohol demand, and alcohol-related consequences in PTS-positive (n = 64) and PTS-negative (n = 200) college students (M age = 21.7; 77% women; 54% Caucasian; 34% African American) who endorsed past-month alcohol use. We tested craving and alcohol demand as mediators of the relation between PTS status and alcohol-related consequences. Craving (B = .04, SE = .02, 95% CI [.01, .10]), demand intensity (B = .02, SE = .02, 95% CI [.001, .07]), and demand elasticity (B = .05, SE = .03, 95% CI [.006, .12]) significantly mediated the association between PTS symptoms and alcohol-related consequences. Craving remained a significant mediator in a multiple mediators model (B = .08, SE = .04, 95% CI [.03, .19]). Craving and alcohol demand may partially explain the relation between PTS status and alcohol-related consequences. Craving may be especially salient for individuals with PTS symptoms, as it may lead to more severe alcohol-related consequences even in the absence of elevated alcohol consumption. (c) 2015 APA, all rights reserved).

Alcohol Craving and Demand Mediate the Relation between Posttraumatic Stress Symptoms and Alcohol-Related Consequences

PubMed Central

Tripp, Jessica C.; Meshesha, Lidia Z.; Teeters, Jenni B.; Pickover, Alison; McDevitt-Murphy, Meghan E.; Murphy, James G.

2015-01-01

Objective Posttraumatic stress (PTS) symptoms are associated with alcohol-related consequences, but there is a need to understand mediators that may help explain the reasons for this relationship. Individuals with PTS may experience elevated craving and alcohol reward value (demand), which may contribute to risk for alcohol-related consequences. Method We examined relationships between PTS status, craving, alcohol demand, and alcohol-related consequences in PTS-positive (n = 64) and PTS-negative (n = 200) college students (M age = 21.7; 77% women; 54% Caucasian; 34% African American) who endorsed past-month alcohol use. We tested craving and alcohol demand as mediators of the relation between PTS status and alcohol problems. Results Craving (B = .04, SE = .02, 95% CI = .01 – .10), demand intensity (B = .05, SE = .03, 95% CI = .0009 – .17), and demand elasticity (B = .05, SE = .03, 95% CI = .006 – .03) significantly mediated the association between PTS symptoms and alcohol problems. Craving remained a significant mediator in a multiple mediators model (B = .08, SE = .04, 95% CI = .03 – .19). Conclusions Craving and alcohol demand may partially explain the relation between PTS status and alcohol-related consequences. Craving may be especially salient for individuals with PTS symptoms, as it may lead to more severe alcohol-related consequences even in the absence of elevated alcohol consumption. PMID:26375513

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

Childhood internalizing symptoms are negatively associated with early adolescent alcohol use

PubMed Central

Edwards, Alexis C.; Latendresse, Shawn J.; Heron, Jon; Cho, Seung Bin; Hickman, Matt; Lewis, Glyn; Dick, Danielle M.; Kendler, Kenneth S.

2014-01-01

Background The relationship between childhood internalizing problems and early adolescent alcohol use has been infrequently explored and remains unclear. Methods We employed growth mixture modeling of internalizing symptoms for a large, population-based sample of UK children (the ALSPAC cohort) to identify trajectories of childhood internalizing symptoms from age 4 through age 11.5. We then examined the relationship between membership in each trajectory and alcohol use in early adolescence (reported at age 13.8). Results Overall, children experiencing elevated levels of internalizing symptoms were less likely to use alcohol in early adolescence. This finding held true across all internalizing trajectories; i.e., those exhibiting increasing levels of internalizing symptoms over time, and those whose symptoms desisted over time, were both less likely to use alcohol than their peers who did not exhibit internalizing problems. Conclusions We conclude that childhood internalizing symptoms, unlike adolescent symptoms, are negatively associated with early adolescent alcohol experimentation. Additional studies are warranted to follow up on our preliminary evidence that symptoms of phobia and separation anxiety drive this effect. PMID:24848214

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.

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

Maternal Depressive Symptoms and Adolescent Alcohol Use: The Mediating Role of Youth Depressive Symptoms

ERIC Educational Resources Information Center

Herman-Stahl, Mindy; Saavedra, Lissette M.; Morgan-Lopez, Antonio A.; Novak, Scott P.; Warner, Tara D.; Fishbein, Diana H.

2017-01-01

The purpose of this study was to explore the influence of maternal depressive symptoms on adolescent alcohol use among a sample of Latino/Latina youth aged 10 to 16 years from a high-risk community. Direct and mediating effects of youth depressive symptoms, controlling for levels of concurrent emotion dysregulation, on alcohol use were examined.…

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.

Acute effects of a guided relaxation routine (body scan) on tobacco withdrawal symptoms and cravings in abstinent smokers.

PubMed

Cropley, Mark; Ussher, Michael; Charitou, Elli

2007-06-01

To examine the acute effects of a guided relaxation routine (body scan) on desire to smoke and tobacco withdrawal symptoms in overnight abstinent smokers. Experimental. Thirty individuals reporting to smoke 10 or more cigarettes daily for at least 3 years. Participants were assigned randomly to complete a 10-minute body scan (experimental group n = 15) or listen to a natural history passage for 10 minutes (control group n = 15). Ratings of strength of desire to smoke and smoking withdrawal symptoms were assessed at baseline, immediately after the interventions, and 5, 10 and 15 minutes post-intervention. There was a significant group x time interaction for strength of desire to smoke. The mean desire to smoke rating was significantly lower in the body scan group relative to the control group immediately after the intervention, and 5 minutes post-intervention. The body scan group also reported lower ratings of irritability, tension and restlessness, relative to the controls. A brief body scan intervention reduces strength of desire to smoke and some tobacco withdrawal symptoms in temporarily abstaining smokers. The body scan may be beneficial as a technique for managing cigarette cravings and withdrawal.

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.

Interactions Between Alcohol Metabolism Genes and Religious Involvement in Association With Maximum Drinks and Alcohol Dependence Symptoms

PubMed Central

Chartier, Karen G.; Dick, Danielle M.; Almasy, Laura; Chan, Grace; Aliev, Fazil; Schuckit, Marc A.; Scott, Denise M.; Kramer, John; Bucholz, Kathleen K.; Bierut, Laura J.; Nurnberger, John; Porjesz, Bernice; Hesselbrock, Victor M.

2016-01-01

Objective: Variations in the genes encoding alcohol dehydrogenase (ADH) enzymes are associated with both alcohol consumption and dependence in multiple populations. Additionally, some environmental factors have been recognized as modifiers of these relationships. This study examined the modifying effect of religious involvement on relationships between ADH gene variants and alcohol consumption–related phenotypes. Method: Subjects were African American, European American, and Hispanic American adults with lifetime exposure to alcohol (N = 7,716; 53% female) from the Collaborative Study on the Genetics of Alcoholism. Genetic markers included ADH1B-rs1229984, ADH1B-rs2066702, ADH1C-rs698, ADH4-rs1042364, and ADH4-rs1800759. Phenotypes were maximum drinks consumed in a 24-hour period and total number of alcohol dependence symptoms according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Religious involvement was defined by self-reported religious services attendance. Results: Both religious involvement and ADH1B-rs1229984 were negatively associated with the number of maximum drinks consumed and the number of lifetime alcohol dependence symptoms endorsed. The interactions of religious involvement with ADH1B-rs2066702, ADH1C-rs698, and ADH4-rs1042364 were significantly associated with maximum drinks and alcohol dependence symptoms. Risk variants had weaker associations with maximum drinks and alcohol dependence symptoms as a function of increasing religious involvement. Conclusions: This study provided initial evidence of a modifying effect for religious involvement on relationships between ADH variants and maximum drinks and alcohol dependence symptoms. PMID:27172571

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. ...

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.

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…

Alcohol Demand, Future Orientation, and Craving Mediate the Relation Between Depressive and Stress Symptoms and Alcohol Problems.

PubMed

Soltis, Kathryn E; McDevitt-Murphy, Meghan E; Murphy, James G

2017-06-01

Elevated depression and stress have been linked to greater levels of alcohol problems among young adults even after taking into account drinking level. This study attempts to elucidate variables that might mediate the relation between symptoms of depression and stress and alcohol problems, including alcohol demand, future time orientation, and craving. Participants were 393 undergraduates (60.8% female, 78.9% White/Caucasian) who reported at least 2 binge-drinking episodes (4/5+ drinks for women/men, respectively) in the previous month. Participants completed self-report measures of stress and depression, alcohol demand, future time orientation, craving, and alcohol problems. In separate mediation models that accounted for gender, race, and weekly alcohol consumption, future orientation and craving significantly mediated the relation between depressive symptoms and alcohol problems. Alcohol demand, future orientation, and craving significantly mediated the relation between stress symptoms and alcohol problems. Heavy-drinking young adults who experience stress or depression are likely to experience alcohol problems, and this is due in part to elevations in craving and alcohol demand, and less sensitivity to future outcomes. Interventions targeting alcohol misuse in young adults with elevated levels of depression and stress should attempt to increase future orientation and decrease craving and alcohol reward value. Copyright © 2017 by the Research Society on Alcoholism.

Mindfulness Is Associated with Fewer PTSD Symptoms, Depressive Symptoms, Physical Symptoms, and Alcohol Problems in Urban Firefighters

ERIC Educational Resources Information Center

Smith, Bruce W.; Ortiz, J. Alexis; Steffen, Laurie E.; Tooley, Erin M.; Wiggins, Kathryn T.; Yeater, Elizabeth A.; Montoya, John D.; Bernard, Michael L.

2011-01-01

Objective: This study investigated the association between mindfulness, other resilience resources, and several measures of health in 124 urban firefighters. Method: Participants completed health measures of posttraumatic stress disorder (PTSD) symptoms, depressive symptoms, physical symptoms, and alcohol problems and measures of resilience…

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

Social interaction and social withdrawal in rodents as readouts for investigating the negative symptoms of schizophrenia

PubMed Central

Wilson, Christina A.; Koenig, James I.

2015-01-01

Negative symptoms (e.g., asociality and anhedonia) are a distinct symptomatic domain that has been found to significantly affect the quality of life in patients diagnosed with schizophrenia. Additionally, the primary negative symptom of asociality (i.e., withdrawal from social contact that derives from indifference or lack of desire to have social contact) is a major contributor to poor psychosocial functioning and has been found to play an important role in the course of the disorder. Nonetheless, the pathophysiology underlying these symptoms is unknown and currently available treatment options (e.g., antipsychotics and cognitive-behavioral therapy) fail to reliably produce efficacious benefits. Utilizing rodent paradigms that measure social behaviors (e.g., social withdrawal) to elucidate the neurobiological substrates that underlie social dysfunction and to identify novel therapeutic targets may be highly informative and useful to understand more about the negative symptoms of schizophrenia. Accordingly, the purpose of this review is to provide an overview of the behavioral tasks for assessing social functioning that may be translationally relevant for investigating negative symptoms associated with schizophrenia. PMID:24342774

Social interaction and social withdrawal in rodents as readouts for investigating the negative symptoms of schizophrenia.

PubMed

Wilson, Christina A; Koenig, James I

2014-05-01

Negative symptoms (e.g., asociality and anhedonia) are a distinct symptomatic domain that has been found to significantly affect the quality of life in patients diagnosed with schizophrenia. Additionally, the primary negative symptom of asociality (i.e., withdrawal from social contact that derives from indifference or lack of desire to have social contact) is a major contributor to poor psychosocial functioning and has been found to play an important role in the course of the disorder. Nonetheless, the pathophysiology underlying these symptoms is unknown and currently available treatment options (e.g., antipsychotics and cognitive-behavioral therapy) fail to reliably produce efficacious benefits. Utilizing rodent paradigms that measure social behaviors (e.g., social withdrawal) to elucidate the neurobiological substrates that underlie social dysfunction and to identify novel therapeutic targets may be highly informative and useful to understand more about the negative symptoms of schizophrenia. Accordingly, the purpose of this review is to provide an overview of the behavioral tasks for assessing social functioning that may be translationally relevant for investigating negative symptoms associated with schizophrenia. © 2013 Published by Elsevier B.V. and ECNP.

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...

Alcohol Demand, Future Orientation, and Craving Mediate the Relation Between Depressive and Stress Symptoms and Alcohol Problems

PubMed Central

Soltis, Kathryn E.; McDevitt-Murphy, Meghan; Murphy, James G.

2017-01-01

Background Elevated depression and stress have been linked to greater levels of alcohol problems among young adults even after taking into account drinking level. The current study attempts to elucidate variables that might mediate the relation between symptoms of depression and stress and alcohol problems, including alcohol demand, future time orientation, and craving. Methods Participants were 393 undergraduates (60.8% female, 78.9% White/Caucasian) who reported at least 2 binge drinking episodes (4/5+ drinks for women/men, respectively) in the previous month. Participants completed self-report measures of stress and depression, alcohol demand, future time orientation, craving, and alcohol problems. Results In separate mediation models that accounted for gender, race, and weekly alcohol consumption, future orientation and craving significantly mediated the relation between depressive symptoms and alcohol problems. Alcohol demand, future orientation, and craving significantly mediated the relation between stress symptoms and alcohol problems. Conclusions Heavy drinking young adults who experience stress or depression are likely to experience alcohol problems and this is due in part to elevations in craving and alcohol demand, and less sensitivity to future outcomes. Interventions targeting alcohol misuse in young adults with elevated levels of depression and stress should attempt to increase future orientation and decrease craving and alcohol reward value. PMID:28401985

ADHD symptoms impact smoking outcomes and withdrawal in response to Varenicline treatment for smoking cessation.

PubMed

Bidwell, L Cinnamon; Karoly, Hollis C; Hutchison, Kent E; Bryan, Angela D

2017-10-01

Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with nicotine dependence and difficulty quitting smoking. Few cessation trials specifically consider the impact of ADHD on treatment outcomes, including those testing established pharmacological therapies, such as varenicline. The current study focused on the impact of pretreatment ADHD inattention (IN) and hyperactivity-impulsivity (HI) symptoms on treatment outcome in a randomized controlled trial of varenicline [N=205, average age=34.13(10.07), average baseline cigarettes per day=14.71(7.06)]. Given that varenicline's putative therapeutic mechanism is attenuation of withdrawal severity during abstinence, we also tested changes in withdrawal as a mediator of treatment effects in high and low ADHD groups. ADHD symptom severity in this sample was in the subclinical range. Cessation was associated with HI, but not IN, such that high HI individuals on varenicline reported the lowest smoking levels at the end of treatment across all groups (3.06cig/day for high HI vs 4.02cig/day for low HI). Individuals with high HI who received placebo had the highest smoking at the end of treatment (7.69cigs/day for high HI vs 5.56cig/day for low HI). Patterns continued at follow-up. Varenicline significantly reduced withdrawal for those with high HI, but not low HI. However, path models did not support an indirect effect of medication on reducing smoking via withdrawal in either group, suggesting that unmeasured variables are involved in varenicline's effect on reducing smoking. These data add to a gap in the smoking cessation literature regarding the impact of ADHD symptoms on the efficacy and mechanisms of frontline pharmacological treatments. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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.

Parent Alcoholism Impacts the Severity and Timing of Children's Externalizing Symptoms

ERIC Educational Resources Information Center

Hussong, Andrea M.; Huang, Wenjing; Curran, Patrick J.; Chassin, Laurie; Zucker, Robert A.

2010-01-01

Although previous studies show that children of alcoholic parents have higher rates of externalizing symptoms compared to their peers, it remains unclear whether the timing of children's externalizing symptoms is linked to that of their parent's alcohol-related symptoms. Using a multilevel modeling approach, we tested whether children aged 2…

BDNF–TrkB signaling in the nucleus accumbens shell of mice has key role in methamphetamine withdrawal symptoms

PubMed Central

Ren, Q; Ma, M; Yang, C; Zhang, J-C; Yao, W; Hashimoto, K

2015-01-01

Depression is a core symptom of methamphetamine (METH) withdrawal during the first several weeks of abstinence. However, the precise mechanisms underlying METH withdrawal symptoms remain unknown. Brain-derived neurotrophic factor (BDNF) and its specific receptor, tropomyosin-related kinase (TrkB), have a role the in pathophysiology of depression. In this study, we examined the role of BDNF–TrkB signaling in different brain regions of male mice with METH withdrawal symptoms. Repeated METH (3 mg kg−1 per day for 5 days) administration to mice caused a long-lasting depression-like behavior including anhedonia. Western blot analysis showed that BDNF levels in the nucleus accumbens (NAc) of METH-treated mice were significantly higher than those of control mice whereas BDNF levels in other regions, including the prefrontal cortex and hippocampus, were not altered. METH-induced depression-like behavior, behavioral sensitization and dendritic changes in the NAc shell were improved by subsequent subchronic administration of TrkB antagonist ANA-12 (0.5 mg kg−1 per day for 14 days), but not TrkB agonist 7,8-dihydroxyflavone (10 mg kg−1 per day for 14 days). In vivo microdialysis showed that METH (1 mg kg−1)-induced dopamine release in NAc shell of METH-treated mice was attenuated after subsequent subchronic ANA-12 administration. Interestingly, a single bilateral infusion of ANA-12 into the NAc shell, but not NAc core, showed a rapid and long-lasting therapeutic effect. However, ketamine and paroxetine had no effect. These findings suggest that increased BDNF–TrkB signaling in the NAc shell has an important role in the behavioral abnormalities after withdrawal from repeated METH administration, and that TrkB antagonists are potential therapeutic drugs for withdrawal symptoms in METH abusers. PMID:26506052

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

Alcohol misuse, depressive symptoms, and HIV/STI risks of US Hispanic women.

PubMed

McCabe, Brian E; Schaefer Solle, Natasha; Peragallo Montano, Nilda; Mitrani, Victoria B

2017-10-01

Alcohol misuse and depressive symptoms have been linked to HIV/STI risk, but studies have rarely included Hispanic women, who have over four times greater HIV incidence than white, non-Hispanic women. Understanding the connections among alcohol misuse, depressive symptoms, and HIV/STI risks may suggest ways to meet specific needs of Hispanic women. This study's objective is to examine the relationships among alcohol misuse, depressive symptoms, and seven HIV/STI risk factors. Five hundred forty-eight US Hispanic women with intake data from a randomized trial were assessed for alcohol misuse (CAGE) and depressive symptoms (CES-D). GZLM and path analyses tested relationships between alcohol misuse or depressive symptoms and HIV/STI risk factors. Self-efficacy and condom use were not related to alcohol misuse or depressive symptoms, but only 15% of women reported consistent condom use. After controlling for demographics, women with alcohol misuse had significantly more perceived HIV/STI risk (OR = 2.15) and better HIV/STI knowledge (β = -.54); and women with depressive symptoms had significantly more perceived HIV/STI risk (OR = 1.76) and worse HIV/STI knowledge (β = .37). Interventions to increase condom use for Hispanic women are needed, regardless of mental disorders. Working with Hispanic women with alcohol misuse or depressive symptoms presents a need (and opportunity) to address issues directly related to HIV/STI risk. Women's health practitioners have an excellent opportunity to reach women by implementing regular screening programs in clinics that serve Hispanic women. For women with high depressive symptoms, poor HIV/STI knowledge should also be addressed. Future studies should test whether integrated and tailored risk reduction interventions affect these factors and lower HIV/STI risk for Hispanic women.

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

Is Homepathy Effective for Hot Flashes and other Estrogen-Withdrawal Symptoms in Breast Cancer Survivors? A Preliminary Randomized Controlled Trial

DTIC Science & Technology

2000-04-01

AD__________ Award Number: DAMD17-99-1-9438 TITLE: Is Homeopathy Effective for Hot Flashes and Other Estrogen-Withdrawal Symptoms in Breast Cancer...Mar 00) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Is Homeopathy Effective for Hot Flashes and Other Estrogen- DAMD17-99-1-9438 Withdrawal Symptoms in...there is evidence that homeopathy is an effective treatment to improve the quality of life in breast cancer survivors who are experiencing hot flashes

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

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.

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.

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

Alcohol, cannabis, nicotine, and caffeine use and symptom distress in schizophrenia.

PubMed

Hamera, E; Schneider, J K; Deviney, S

1995-09-01

The high prevalence of substance use, e.g., alcohol and illegal and nonprescribed drugs, in schizophrenia is widely recognized. One explanation for this high prevalence is that substance use may be a self-initiated method for managing symptoms. To test whether the intake of four substances--alcohol, cannabis, nicotine, and caffeine--would increase with increases in symptom distress, daily self-reports of symptom distress and substance intake over 12 weeks were analyzed with pooled time series analyses. Compliance with neuroleptic medication was added to the analyses to control for any changes in prescribed medication compliance while using nonprescribed drugs or alcohol. Of the four substances studied, only nicotine was significantly related to symptom distress. Higher distress with prodromal symptoms was related to decreases in nicotine use. Analysis of caffeine did not meet the criteria for significance but does provide direction for further research. Higher distress, with neurotic symptoms, was related to increases in caffeine use. Further research is needed to clarify the relationship between nicotine and symptoms.

The impact of sleep and psychiatric symptoms on alcohol consequences among young adults.

PubMed

Miller, Mary Beth; Van Reen, Eliza; Barker, David H; Roane, Brandy M; Borsari, Brian; McGeary, John E; Seifer, Ronald; Carskadon, Mary A

2017-03-01

Independent lines of research have documented links between psychiatric symptoms and poor sleep quality, psychiatric symptoms and alcohol use, and alcohol use and poor sleep quality. The current study examined the synergistic effect of poor sleep quality and psychiatric symptoms on alcohol-related consequences in heavy-drinking young adults. Matriculating college students reporting at least one heavy drinking episode over the first nine weeks of the semester (N=385, 52% female) were categorized as experiencing 'good' (n=280) versus 'poor' sleep quality (n=105) and screening 'positive' (n=203) or 'negative' (n=182) for a psychiatric disorder. Sleep quality was assessed using the Pittsburgh Sleep Quality Index; psychiatric diagnosis was assessed using the Psychiatric Diagnostic Screening Questionnaire; and alcohol-related consequences were assessed using the Brief Young Adult Alcohol Consequences Questionnaire. General linear models were used to examine the main effects and interaction between sleep quality and psychiatric symptoms on alcohol-related consequences. Sleep quality moderated the association between psychiatric screen and alcohol-related consequences among heavy-drinking college students, such that psychiatric symptoms were associated with more alcohol-related consequences in the context of poor sleep quality. The combination of poor sleep quality and psychiatric symptoms is associated with increased alcohol-related consequences among heavy-drinking college students. Given the significant interaction between these symptoms, healthcare providers are encouraged to screen for the presence of sleep and psychiatric disorders among heavy-drinking young adults and to provide empirically-supported treatments as appropriate. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

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.

Impulsivity interacts with momentary PTSD symptom worsening to predict alcohol use in male veterans.

PubMed

Black, Anne C; Cooney, Ned L; Sartor, Carolyn E; Arias, Albert J; Rosen, Marc I

2018-04-11

Posttraumatic stress disorder (PTSD) is prevalent among veterans who served post-9/11, and co-occurs with problem alcohol and substance use. Studies using ecological momentary assessment have examined the temporal association between time-varying PTSD symptoms and alcohol use. Results suggest individual differences in these associations. We tested hypotheses that alcohol use measured by momentary assessment would be explained by acute increases in PTSD symptoms, and the PTSD-alcohol association would be moderated by trait impulsivity. A sample of 28 male post-9/11-era veterans who reported past-month PTSD symptoms and risky alcohol use were enrolled. On a quasi-random schedule, participants completed three electronic assessments daily for 28 days measuring past 2-h PTSD symptoms, alcohol, and substance use. At baseline, trait impulsivity was measured by the Barratt Impulsiveness Scale. Past-month PTSD symptoms and alcohol use were measured. Using three-level hierarchical models, number of drinks recorded by momentary assessment was modeled as a function of change in PTSD symptoms since last assessment, controlling for lag-1 alcohol and substance use and other covariates. A cross-level interaction tested moderation of the within-time PTSD-alcohol association by impulsivity. A total of 1,522 assessments were completed. A positive within-time association between PTSD symptom change and number of drinks was demonstrated. The association was significantly moderated by impulsivity. Results provide preliminary support for a unique temporal relationship between acute PTSD symptom change and alcohol use among veterans with trait impulsiveness. If replicated in a clinical sample, results may have implications for a targeted momentary intervention.

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

Sleep, Internalizing Problems, and Social Withdrawal: Unique Associations in Clinic-Referred Youth With Elevated Sluggish Cognitive Tempo Symptoms.

PubMed

Rondon, Ana T; Hilton, Dane C; Jarrett, Matthew A; Ollendick, Thomas H

2018-02-01

We compared clinic-referred youth with ADHD + sluggish cognitive tempo (SCT; n = 34), ADHD Only ( n = 108), and SCT Only ( n = 22) on demographics, co-occurring symptomatology, comorbid diagnoses, and social functioning. In total, 164 youth (age = 6-17 years, M = 9.97) and their parent(s) presented to an outpatient clinic for a psychoeducational assessment. Between-group analyses and regressions were used to examine study variables. SCT groups were older and exhibited more parent-reported internalizing problems, externalizing problems, sleep problems, and social withdrawal on the Child Behavior Checklist. No significant differences emerged between groups on the Teacher Report Form. Regression analyses involving multiple covariates revealed that SCT symptoms were uniquely related to social withdrawal but not general social problems. Based on parent report, SCT symptoms have a unique relationship with internalizing problems, sleep problems, and social withdrawal. Future research should explore correlates of SCT in youth using multiple informants.

Symptoms of Depression and PTSD are Associated with Elevated Alcohol Demand

PubMed Central

Murphy, James G.; Yurasek, Ali M.; Dennhardt, Ashley A.; Skidmore, Jessica R.; McDevitt-Murphy, Meghan E.; MacKillop, James; Martens, Matthew P.

2013-01-01

BACKGROUND Behavioral economic demand curves measure individual differences in motivation for alcohol and have been associated with problematic patterns of alcohol use, but little is known about the variables that may contribute to elevated demand. Negative visceral states have been theorized to increase demand for alcohol and to contribute to excessive drinking patterns, but little empirical research has evaluated this possibility. The present study tested the hypothesis that symptoms of depression and PTSD would be uniquely associated with elevated alcohol demand even after taking into account differences in typical drinking levels. METHOD An Alcohol Purchase Task (APT) was used to generate a demand curve measure of alcohol reinforcement in a sample of 133 college students (50.4% male, 64.4% Caucasian, 29.5% African-American) who reported at least one heavy drinking episode (5/4 or more drinks in one occasion for a man/woman) in the past month. Participants also completed standard measures of alcohol consumption and symptoms of depression and PTSD. RESULTS Regression analyses indicated that symptoms of depression were associated with higher demand intensity (alcohol consumption when price = 0; ΔR2 = .05, p = .002) and lower elasticity (ΔR2 = .04, p = .03), and that PTSD symptoms were associated with all five demand curve metrics (ΔR2 = .04 – .07, ps < .05). CONCLUSIONS These findings provide support for behavioral economic models of addiction that highlight the role of aversive visceral states in increasing the reward value of alcohol and provide an additional theoretical model to explain the association between negative affect and problematic drinking patterns. PMID:22809894

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

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.

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

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

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

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

Development of personal narratives as a mediator of the impact of deficits in social cognition and social withdrawal on negative symptoms in schizophrenia.

PubMed

Lysaker, Paul H; Erikson, Molly; Macapagal, Kathryn R; Tunze, Chloe; Gilmore, Emily; Ringer, Jamie M

2012-04-01

Although negative symptoms are a barrier to recovery from schizophrenia, little is understood about the psychological processes that reinforce and sustain them. To explore this issue, this study used structural equation modeling to test whether the impact of social withdrawal and emotion recognition deficits upon negative symptoms is mediated by the richness or poverty of personal narratives. The participants were 99 adults with schizophrenia spectrum disorders. Social cognition was assessed using the Bell-Lysaker Emotional Recognition Task; social withdrawal, using the Quality of Life Scale; narrative coherence, using the Scale To Assess Narrative Development; and negative symptoms, using the Positive and Negative Syndrome Scale. The findings reveal that although social cognition deficits and social withdrawal are significantly associated with negative symptom severity, these relationships become nonsignificant when personal narrative integrity is examined as a mediating factor. These results indicate that the development of personal narratives may be directly linked to the severity of negative symptoms; this construct may be a useful target for future interventions.

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

Obsessive-compulsive symptoms and negative affect during tobacco withdrawal in a non-clinical sample of African American smokers.

PubMed

Bello, Mariel S; Pang, Raina D; Chasson, Gregory S; Ray, Lara A; Leventhal, Adam M

2017-05-01

The association between obsessive-compulsive (OC) symptomatology and smoking is poorly understood, particularly in African Americans-a group subject to smoking- and OC-related health disparities. In a non-clinical sample of 253 African American smokers, we tested the negative reinforcement model of OC-smoking comorbidity, purporting that smokers with higher OC symptoms experience greater negative affect (NA) and urge to smoke for NA suppression upon acute tobacco abstinence. Following a baseline visit involving OC assessment, participants completed two counterbalanced experimental visits (non-abstinent vs. 16-h tobacco abstinence) involving affect, smoking urge, and nicotine withdrawal assessment. OC symptom severity predicted larger abstinence-provoked increases in overall NA, anger, anxiety, depression, fatigue, urge to smoke to suppress NA, and composite nicotine withdrawal symptom index. African American smokers with elevated OC symptoms appear to be vulnerable to negative reinforcement-mediated smoking motivation and may benefit from cessation treatments that diminish NA or the urge to quell NA via smoking. Copyright © 2016 Elsevier Ltd. All rights reserved.

Obsessive-Compulsive Symptoms and Negative Affect During Tobacco Withdrawal in a Non-Clinical Sample of African American Smokers

PubMed Central

Bello, Mariel S.; Pang, Raina D.; Chasson, Gregory S.; Ray, Lara A.; Leventhal, Adam M.

2016-01-01

The association between obsessive-compulsive (OC) symptomatology and smoking is poorly understood, particularly in African Americans—a group subject to smoking- and OC-related health disparities. In a non-clinical sample of 253 African American smokers, we tested the negative reinforcement model of OC-smoking comorbidity, purporting that smokers with higher OC symptoms experience greater negative affect (NA) and urge to smoke for NA suppression upon acute tobacco abstinence. Following a baseline visit involving OC assessment, participants completed two counterbalanced experimental visits (non-abstinent vs. 16-hr tobacco abstinence) involving affect, smoking urge, and nicotine withdrawal assessment. OC symptom severity predicted larger abstinence-provoked increases in overall NA, anger, anxiety, depression, fatigue, urge to smoke to suppress NA, and composite nicotine withdrawal symptom index. African American smokers with elevated OC symptoms appear to be vulnerable to negative reinforcement-mediated smoking motivation and may benefit from cessation treatments that diminish NA or the urge to quell NA via smoking. PMID:27769664

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�

Infants' social withdrawal symptoms assessed with a direct infant observation method in primary health care.

PubMed

Puura, Kaija; Mäntymaa, Mirjami; Luoma, Ilona; Kaukonen, Pälvi; Guedeney, Antoine; Salmelin, Raili; Tamminen, Tuula

2010-12-01

Distressed infants may withdraw from social interaction, but recognising infants' social withdrawal is difficult. The aims of the study were to see whether an infant observation method can be reliably used by front line workers, and to examine the prevalence of infants' social withdrawal symptoms. A random sample of 363 families with four, eight or 18-month-old infants participated in the study. The infants were examined by general practitioners (GPs) in well-baby clinics with the Alarm Distress BaBy Scale (ADBB), an observation method developed for clinical settings. A score of five or more on the ADBB Scale in two subsequent assessments at a two-week interval was regarded as a sign of clinically significant infant social withdrawal. Kappas were calculated for the GPs' correct rating of withdrawn/not withdrawn against a set of videotapes rated by developer of the method, Professor Guedeney and his research group. The kappas for their ratings ranged from 0.5 to 1. The frequency of infants scoring above the cut off in two subsequent assessments was 3%. The ADBB Scale is a promising method for detecting infant social withdrawal in front line services. Three percents of infants were showing sustained social withdrawal as a sign of distress in this normal population sample. Copyright © 2010 Elsevier Inc. All rights reserved.

Symptoms of depression and PTSD are associated with elevated alcohol demand.

PubMed

Murphy, James G; Yurasek, Ali M; Dennhardt, Ashley A; Skidmore, Jessica R; McDevitt-Murphy, Meghan E; MacKillop, James; Martens, Matthew P

2013-01-01

Behavioral economic demand curves measure individual differences in motivation for alcohol and have been associated with problematic patterns of alcohol use, but little is known about the variables that may contribute to elevated demand. Negative visceral states have been theorized to increase demand for alcohol and to contribute to excessive drinking patterns, but little empirical research has evaluated this possibility. The present study tested the hypothesis that symptoms of depression and PTSD would be uniquely associated with elevated alcohol demand even after taking into account differences in typical drinking levels. An Alcohol Purchase Task (APT) was used to generate a demand curve measure of alcohol reinforcement in a sample of 133 college students (50.4% male, 64.4% Caucasian, 29.5% African-American) who reported at least one heavy drinking episode (5/4 or more drinks in one occasion for a man/woman) in the past month. Participants also completed standard measures of alcohol consumption and symptoms of depression and PTSD. Regression analyses indicated that symptoms of depression were associated with higher demand intensity (alcohol consumption when price=0; ΔR(2)=.05, p=.002) and lower elasticity (ΔR(2)=.04, p=.03), and that PTSD symptoms were associated with all five demand curve metrics (ΔR(2)=.04-.07, ps<.05). These findings provide support for behavioral economic models of addiction that highlight the role of aversive visceral states in increasing the reward value of alcohol and provide an additional theoretical model to explain the association between negative affect and problematic drinking patterns. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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

Effect of Opuntia ficus indica on symptoms of the alcohol hangover.

PubMed

Wiese, Jeff; McPherson, Steve; Odden, Michelle C; Shlipak, Michael G

2004-06-28

The severity of the alcohol hangover may be related to inflammation induced by impurities in the alcohol beverage and byproducts of alcohol metabolism. An extract of the Opuntia ficus indica (OFI) plant diminishes the inflammatory response to stressful stimuli. In this double-blind, placebo-controlled, crossover trial, 64 healthy, young adult volunteers were randomly assigned to receive OFI (1600 IU) and identical placebo, given 5 hours before alcohol consumption. During 4 hours, subjects consumed up to 1.75 g of alcohol per kilogram of body weight. Hangover severity (9 symptoms) and overall well-being were assessed on a scale (0-6), and blood and urine samples were obtained the following morning. Two weeks later, the study protocol was repeated with OFI and placebo reversed. Fifty-five subjects completed both the OFI and placebo arms of the study. Three of the 9 symptoms-nausea, dry mouth, and anorexia-were significantly reduced by OFI (all P<.05). Overall, the symptom index was reduced by 2.7 points on average (95% confidence interval, -0.2 to 5.5; P =.07), and the risk of a severe hangover (>/=18 points) was reduced by half (odds ratio, 0.38; 95% confidence interval, 0.16-0.88; P =.02). C-reactive protein levels were strongly associated with hangover severity; the mean symptom index was 4.1 (95% confidence interval, 1.2-7.1; P =.007) higher in subjects with morning C-reactive protein levels greater than 1.0 mg/L. In addition, C-reactive protein levels were 40% higher after subjects consumed placebo compared with OFI. The symptoms of the alcohol hangover are largely due to the activation of inflammation. An extract of the OFI plant has a moderate effect on reducing hangover symptoms, apparently by inhibiting the production of inflammatory mediators.

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.

Depressive symptoms and alcohol correlates among Brazilians aged 14 years and older: a cross-sectional study

PubMed Central

2014-01-01

Background The associations between depressive symptoms and alcohol-related disorders, drinking patterns and other characteristics of alcohol use are important public health issues worldwide. This study aims to study these associations in an upper middle-income country, Brazil, and search for related socio-demographic correlations in men and women. Methods A cross-sectional study was conducted between November 2005 and April 2006. The sample of 3,007 participants, selected using a multistage probabilistic sampling method, represents the Brazilian population aged 14 and older. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale and alcohol dependence was assessed using the Composite International Diagnostic Interview. Associations assessed using bi-variate analysis were tested using Rao-Scott measures. Gender specific multinomial logistic regression models were developed. Results Among the participants with alcohol dependence, 46% had depressive symptoms (17.2% mild/moderate and 28.8% major/severe; p < 0.01); 35.8% (p = 0.08) of those with alcohol abuse and 23.9% (p < 0.01) of those with a binge-drinking pattern also had depressive symptoms. Alcohol abstainers and infrequent drinkers had the highest prevalence of major/severe depressive symptoms, whereas frequent heavy drinkers had the lowest prevalence of major/severe depressive symptoms. In women, alcohol dependence and the presence of one or more problems related to alcohol consumption were associated with higher risks of major/severe depressive symptoms. Among men, alcohol dependence and being ≥45 years old were associated with higher risks of major/severe depressive symptoms. Conclusions In Brazil, the prevalence of depressive symptoms is strongly related to alcohol dependence; the strongest association was between major/severe depressive symptoms and alcohol dependence in women. This survey supports the possible association of biopsychosocial distress

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.

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.

Quantifying alcohol consumption: Self-report, transdermal assessment, and prediction of dependence symptoms.

PubMed

Simons, Jeffrey S; Wills, Thomas A; Emery, Noah N; Marks, Russell M

2015-11-01

Research on alcohol use depends heavily on the validity of self-reported drinking. The present paper presents data from 647 days of self-monitoring with a transdermal alcohol sensor by 60 young adults. We utilized a biochemical measure, transdermal alcohol assessment with the WrisTAS, to examine the convergent validity of three approaches to collecting daily self-report drinking data: experience sampling, daily morning reports of the previous night, and 1-week timeline follow-back (TLFB) assessments. We tested associations between three pharmacokinetic indices (peak concentration, area under the curve (AUC), and time to reach peak concentration) derived from the transdermal alcohol signal and within- and between- person variation in alcohol dependence symptoms. The WrisTAS data corroborated 85.74% of self-reported drinking days based on the experience sampling data. The TLFB assessment and combined experience sampling and morning reports agreed on 87.27% of drinking days. Drinks per drinking day did not vary as a function of wearing or not wearing the sensor; this indicates that participants provided consistent reports of their drinking regardless of biochemical verification. In respect to self-reported alcohol dependence symptoms, the AUC of the WrisTAS alcohol signal was associated with dependence symptoms at both the within- and between- person level. Furthermore, alcohol dependence symptoms at baseline predicted drinking episodes characterized in biochemical data by both higher peak alcohol concentration and faster time to reach peak concentration. The results support the validity of self-report alcohol data, provide empirical data useful for optimal design of daily process sampling, and provide an initial demonstration of the use of transdermal alcohol assessment to characterize drinking dynamics associated with risk for alcohol dependence. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Prospective Association Between Internalizing Symptoms and Adolescent Alcohol Involvement and the Moderating Role of Age and Externalizing Symptoms.

PubMed

Colder, Craig R; Shyhalla, Kathleen; Frndak, Seth; Read, Jennifer P; Lengua, Liliana J; Hawk, Larry W; Wieczorek, William F

2017-12-01

As predicted by self-medication theories that drinking is motivated by a desire to ameliorate emotional distress, some studies find internalizing symptoms (e.g., anxiety, depression) increase risk of adolescent drinking; however, such a risk effect has not been supported consistently. Our prior work examined externalizing symptoms as a potential moderator of the association between internalizing symptoms and adolescent alcohol use to explain some of the inconsistencies in the literature. We found that internalizing symptoms were protective against early adolescent alcohol use particularly for youth elevated on externalizing symptoms (a 2-way interaction). Our sample has now been followed for several additional assessments that extend into young adulthood, and the current study tests whether the protective effect of internalizing symptoms may change as youth age into young adulthood, and whether this age-moderating effect varied across different clusters of internalizing symptoms (social anxiety, generalized anxiety, and depression). Internalizing symptoms were hypothesized to shift from a protective factor to a risk factor with age, particularly for youth elevated on externalizing symptoms. A community sample of 387 adolescents was followed for 9 annual assessments (mean age = 12.1 years at the first assessment and 55% female). Multilevel cross-lagged 2-part zero-inflated Poisson models were used to test hypotheses. The most robust moderating effects were for levels of alcohol use, such that the protective effect of all internalizing symptom clusters was most evident in the context of moderate to high levels of externalizing problems. A risk effect of internalizing symptoms was evident at low levels of externalizing symptoms. With age, the risk and protective effects of internalizing symptoms were evident at less extreme levels of externalizing behavior. With respect to alcohol-related problems, findings did not support age moderation for generalized anxiety or

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

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.

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...

The influence of depressive symptoms on alcohol use among HIV-infected Russian drinkers.

PubMed

Palfai, T P; Cheng, D M; Coleman, S M; Bridden, C; Krupitsky, E; Samet, J H

2014-01-01

Depressive symptoms have been linked to HIV progression through a number of biobehavioral mechanisms including increased alcohol use. Although research supports an association between alcohol use and depressive symptoms among HIV patients, there have been few studies that have examined whether depressive symptoms predict subsequent drinking, especially among heavy drinking HIV-infected patients. Heavy drinking Russian HIV-infected patients (n=700) were recruited from addiction and HIV care settings for a randomized controlled trial of a risk reduction intervention [HERMITAGE]. GEE overdispersed Poisson regression analyses were conducted to assess the association between depressive symptoms and alcohol consumption 6-months later. In adjusted analyses, depressive symptom severity was significantly associated with drinks per day (global p=.02). Compared to the non-depressed category, mild depressive symptoms were significantly associated with more drinks per day [IRR=1.55, (95% CI: 1.14, 2.09)], while moderate [IRR=1.14, (95% CI: 0.83, 1.56)] and severe [IRR=1.48, (95% CI: 0.93, 2.34)] depressive symptoms were not. Associations between depressive symptom severity and heavy drinking days were not statistically significant (global p=.19). Secondary analyses using the BDI-II screening threshold (BDI-II>14) and the BDI-II cognitive subscale suggested an association between depressive symptoms and drinks per day over time but not heavy episodic drinking. Among heavy drinking HIV-infected patients, elevated depressive symptoms were associated with greater subsequent alcohol use. These findings suggest that depressive symptoms may be important to address in efforts to reduce alcohol-related risks among HIV-infected populations. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Placebo caffeine reduces withdrawal in abstinent coffee drinkers.

PubMed

Mills, Llewellyn; Boakes, Robert A; Colagiuri, Ben

2016-04-01

Expectancies have been shown to play a role in the withdrawal syndrome of many drugs of addiction; however, no studies have examined the effects of expectancies across a broad range of caffeine withdrawal symptoms, including craving. The purpose of the current study was to use caffeine as a model to test the effect of expectancy on withdrawal symptoms, specifically whether the belief that one has ingested caffeine is sufficient to reduce caffeine withdrawal symptoms and cravings in abstinent coffee drinkers. We had 24-h abstinent regular coffee drinkers complete the Caffeine Withdrawal Symptom Questionnaire (CWSQ) before and after receiving decaffeinated coffee. One-half of the participants were led to believe the coffee was regular caffeinated coffee (the 'Told Caffeine' condition) and one-half were told that it was decaffeinated (the 'Told Decaf' condition). Participants in the Told Caffeine condition reported a significantly greater reduction in the factors of cravings, fatigue, lack of alertness and flu-like feelings of the CWSQ, than those in the Told Decaf condition. Our results indicated that the belief that one has consumed caffeine can affect caffeine withdrawal symptoms, especially cravings, even when no caffeine was consumed. © The Author(s) 2016.

Selective neurocognitive deficits and poor life functioning are associated with significant depressive symptoms in alcoholism-HIV infection comorbidity.

PubMed

Sassoon, Stephanie A; Rosenbloom, Margaret J; Fama, Rosemary; Sullivan, Edith V; Pfefferbaum, Adolf

2012-09-30

Alcoholism, HIV, and depressive symptoms frequently co-occur and are associated with impairment in cognition and life function. We administered the Beck Depression Inventory-II (BDI-II), measures of life function, and neurocognitive tests to 67 alcoholics, 56 HIV+ patients, 63 HIV+ alcoholics, and 64 controls to examine whether current depressive symptom level (significant, BDI-II>14 vs. minimal, BDI-II<14) was associated with poorer cognitive or psychosocial function in alcoholism-HIV comorbidity. Participants with significant depressive symptoms demonstrated slower manual motor speed and poorer visuospatial memory than those with minimal depressive symptoms. HIV patients with depressive symptoms showed impaired manual motor speed. Alcoholics with depressive symptoms showed impaired visuospatial memory. HIV+ alcoholics with depressive symptoms reported the poorest quality of life; alcoholics with depressive symptoms, irrespective of HIV status, had poorest life functioning. Thus, significant depressive symptoms were associated with poorer selective cognitive and life functioning in alcoholism and in HIV infection, even though depressive symptoms had neither synergistic nor additive effects on cognition in alcoholism-HIV comorbidity. The results suggest the relevance of assessing and treating current depressive symptoms to reduce cognitive compromise and functional disability in HIV infection, alcoholism, and their comorbidity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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.

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.

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.

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.

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

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

Activation of serotonin 5-HT(2C) receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice.

PubMed

Wu, Xian; Pang, Gang; Zhang, Yong-Mei; Li, Guangwu; Xu, Shengchun; Dong, Liuyi; Stackman, Robert W; Zhang, Gongliang

2015-10-21

Abuse and dependence to heroin has evolved into a global epidemic as a significant clinical and societal problem with devastating consequences. Repeated exposure to heroin can induce long-lasting behavioral sensitization and withdrawal. Pharmacological activation of 5-HT2C receptors (5-HT2CRs) suppresses psychostimulant-induced drug-seeking and behavioral sensitization. The present study examined the effect of a selective 5-HT2CR agonist lorcaserin on behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice. Male mice received heroin (1.0 mg/kg, s.c.) twice a day for 3 days and then drug treatment was suspended for 5 days. On day 9, a challenge dose of heroin (1.0 mg/kg) was administered to examine the expression of behavioral sensitization. Lorcaserin administered during the development, withdrawal or expression stage suppressed heroin-induced behavioral sensitization on day 9. Another cohort of mice received increasing doses of heroin over a 4.5-day period. Lorcaserin, or the positive control clonidine (an α2-adrenoceptor agonist) suppressed naloxone-precipitated withdrawal symptoms in heroin-treated mice. These findings suggest that activation of 5-HT2CRs suppresses behavioral sensitization and withdrawal in heroin-treated mice. Thus, pharmacological activation of 5-HT2CRs may represent a new avenue for the treatment of heroin addiction. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Activation of serotonin 5-HT2C receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice

PubMed Central

Li, Guangwu; Xu, Shengchun; Dong, Liuyi; Stackman, Robert W.; Zhang, Gongliang

2015-01-01

Abuse and dependence to heroin has evolved into a global epidemic as a significant clinical and societal problem with devastating consequences. Repeated exposure to heroin can induce long-lasting behavioral sensitization and withdrawal. Pharmacological activation of 5-HT2C receptors (5-HT2CRs) suppresses psychostimulant-induced drug-seeking and behavioral sensitization. The present study examined the effect of a selective 5-HT2CR agonist lorcaserin on behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice. Male mice received heroin (1.0 mg/kg, s.c.) twice a day for 3 days and then drug treatment was suspended for 5 days. On day 9, a challenge dose of heroin (1.0 mg/kg) was administered to examine the expression of behavioral sensitization. Lorcaserin administered during the development, withdrawal or expression stage suppressed heroin-induced behavioral sensitization on day 9. Another cohort of mice received increasing doses of heroin over a 4.5-day period. Lorcaserin, or the positive control clonidine (an α2-adrenoceptor agonist) suppressed naloxone-precipitated withdrawal symptoms in heroin-treated mice. These findings suggest that activation of 5-HT2CRs suppresses behavioral sensitization and withdrawal in heroin-treated mice. Thus, pharmacological activation of 5-HT2CRs may represent a new avenue for the treatment of heroin addiction. PMID:26375926

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...

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

Nicotine Withdrawal; Measure Your Symptoms (Quiz)

MedlinePlus

... Challenges When Quitting Nicotine Withdrawal Cravings & Triggers Handling Stress Manage Your Mood Weight Gain & Appetite Stay Smokefree for Good Stick with It Weight Management Eat Healthy Get ...

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.

Race-Specific Associations Between Trauma Cognitions and Symptoms of Alcohol Dependence in Individuals with Comorbid PTSD and Alcohol Dependence

PubMed Central

Williams, Monnica; Jayawickreme, Nuwan; Sposato, Rosanna; Foa, Edna B.

2011-01-01

Posttraumatic Stress Disorder (PTSD) changes the way people think about themselves, others, and the safety of the world. These cognitions may play a role in alcohol dependence, where alcohol dependence is maintained as an attempt to manage posttraumatic anxiety. The current study examined black-white differences in various PTSD cognitions and their relationship to symptoms of alcohol dependence in a dually diagnosed sample (N=167). Analyses revealed racial differences in trauma cognitions and their impact on symptoms of alcohol dependence, suggesting that trauma cognitions are more strongly associated with adverse consequences of drinking and alcohol craving severity among African Americans than European Americans. Additional relationships between ethnic identification and trauma-related cognitions are described and theoretical and clinical implications of these findings are discussed. PMID:21930346

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.

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.

Measurement of nicotine withdrawal symptoms: linguistic validation of the Wisconsin Smoking Withdrawal Scale (WSWS) in Malay.

PubMed

Awaisu, Ahmed; Samsudin, Sulastri; Amir, Nur A; Omar, Che G; Hashim, Mohd I; Mohamad, Mohamed H Nik; Shafie, Asrul A; Hassali, Mohamed A

2010-05-22

The purpose of the linguistic validation of the Wisconsin Smoking Withdrawal Scale (WSWS) was to produce a translated version in Malay language which was "conceptually equivalent" to the original U.S. English version for use in clinical practice and research. A seven-member translation committee conducted the translation process using the following methodology: production of two independent forward translations; comparison and reconciliation of the translations; backward translation of the first reconciled version; comparison of the original WSWS and the backward version leading to the production of the second reconciled version; pilot testing and review of the translation, and finalization. Linguistic and conceptual issues arose during the process of translating the instrument, particularly pertaining to the title, instructions, and some of the items of the scale. In addition, the researchers had to find culturally acceptable equivalents for some terms and idiomatic phrases. Notable among these include expressions such as "irritability", "feeling upbeat", and "nibbling on snacks", which had to be replaced by culturally acceptable expressions. During cognitive debriefing and clinician's review processes, the Malay translated version of WSWS was found to be easily comprehensible, clear, and appropriate for the smoking withdrawal symptoms intended to be measured. We applied a rigorous translation method to ensure conceptual equivalence and acceptability of WSWS in Malay prior to its utilization in research and clinical practice. However, to complete the cultural adaptation process, future psychometric validation is planned to be conducted among Malay speakers.

[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.

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...

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...

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

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...

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...

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.

Mothers' Early Depressive Symptoms and Children's First-Grade Adjustment: A Transactional Analysis of Child Withdrawal as a Mediator

ERIC Educational Resources Information Center

Yan, Ni; Dix, Theodore

2014-01-01

Background: The depression-inhibition hypothesis suggests that mothers' depressive symptoms undermine development because they lead children to withdraw from social contact. To test this, this study examined whether poor first-grade adjustment among children of mothers with depressive symptoms is mediated by the emergence of child withdrawal…

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.

Development of Alcohol and Drug Use in Youth With Manic Symptoms.

PubMed

Horwitz, Sarah McCue; Storfer-Isser, Amy; Young, Andrea S; Youngstrom, Eric A; Taylor, H Gerry; Frazier, Thomas W; Arnold, L Eugene; Fristad, Mary A; Birmaher, Boris; Findling, Robert L

2017-02-01

This analysis examined alcohol and drug use over a 6-year follow-up of children in the Longitudinal Assessment of Manic Symptoms (LAMS) study. LAMS screened 6- to 12.9-year-old children visiting 9 child outpatient mental health (MH) clinics, using the Parent General Behavior Inventory 10-item mania scale. All children with scores ≥12 and a matched group with scores ≤12 were invited to enroll. Children were assessed every 6 months. Assessments included demographics, family, MH history, child diagnoses, child stress, and alcohol and drug use. Univariate, bivariate, and interval censored survival analyses were conducted. Of those >9 years at baseline, 34.9% used alcohol at least once, with 11.9% regular users; 30.1% used drugs at least once, with 16.2% regular users. Predictors of any alcohol use were parental marital status, older age at study entry, a primary diagnosis of disruptive behavior disorders at baseline, and number of impactful child life events. Predictors of regular alcohol use included parental marital status, age, and sustained high mania symptoms over the first 24 months of follow-up. Predictors of any drug use were single parent, parental substance use, and stressful child life events. Predictors of regular drug use were parental marital status, stressful child life events, and a baseline disruptive behavior disorder diagnosis. Baseline medications decreased the risk of regular drug use. Longitudinal data on youth with elevated manic symptoms suggest that comorbid disruptive behavior disorder, manic symptom burden, family environment, and stress are predictors of initiation and regular use of substances. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Diagnostic Criteria for Cannabis Withdrawal Syndrome

PubMed Central

Gorelick, David A.; Levin, Kenneth H.; Copersino, Marc L.; Heishman, Stephen J.; Liu, Fang; Boggs, Douglas L.; Kelly, Deanna L.

2011-01-01

Objective Cannabis withdrawal occurs in frequent users who quit, but there are no accepted diagnostic criteria for a cannabis withdrawal syndrome (CWS). This study evaluated diagnostic criteria for CWS proposed in DSM-V and two earlier proposals. Method A convenience sample of 384 adult, non-treatment-seeking lifetime cannabis smokers provided retrospective self-report data on their “most difficult” quit attempt without formal treatment, which was used in this secondary analysis. Prevalence, time of onset, and peak intensity (5-point Likert scale) for 39 withdrawal symptoms (drawn from the literature) were assessed via computer-administered questionnaire. Subject groups were compared using chi-square or ANOVA. Symptom clustering was evaluated with principal components analysis. Results 40.9% of subjects met the DSM-V criterion of ≥ 3 symptoms from a list of 7. There were no associations with sex, race, or type of cannabis preparation used. There were significant positive associations between duration or frequency of cannabis use prior to the quit attempt and experiencing CWS. Subjects with CWS had a significantly shorter duration of abstinence. Alternative syndromal criteria (dropping physical symptoms from DSM-V list; requiring ≥ 2or ≥ 4 symptoms from a list of 11) yielded a similar prevalence of CWS and similar associations with prior cannabis use and relapse. The PCA yielded 12 factors, including some symptom clusters not included in DSM-V. Conclusions Findings support the concurrent and predictive validity of the proposed DSM-V CWS, but suggest that the list of withdrawal symptoms and number required for diagnosis warrant further evaluation. PMID:22153944

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.

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

Genetic and environmental contributions to age of onset of alcohol dependence symptoms in male twins.

PubMed

Liu, I-Chao; Blacker, Deborah L; Xu, Ronghui; Fitzmaurice, Garrett; Tsuang, Ming T; Lyons, Michael J

2004-11-01

To investigate genetic and environmental influences on the development of specific alcohol dependence symptoms. A classical twin study of 3372 male-male twin pairs in the Vietnam Era Twin (VET) Registry based on telephone interviews about alcohol use. The nine diagnostic symptoms according to the Diagnostic and Statistical Manual of Mental Disorder, version III (revised) (DSM-III-R) definition of alcohol dependence. Symptoms were grouped into those based on impaired control, biological effects and social consequences (Beresford's classification) or early versus late symptoms (Nelson's classification). Survival models with random effects were used to examine the age of onset of each symptom. Approximately 38% of the variation in age of onset of each symptom group based on Beresford's classification is due to additive genetic factors. The age of onset of late symptoms from Nelson's classification appears to be most affected by genetic factors. Estimates of genetic effects for impaired control symptoms are greatly decreased when twins with comorbid psychiatric disorders are excluded. Our results support the heritability of age of onset of DSM-III-R-defined symptoms for alcohol dependence. However, no symptom group in Beresford's classification could be identified as more heritable than other symptom groups. A strong association between genetic vulnerability and co-occurring diseases for symptoms indicative of impaired control could be found. In addition, our findings show that the late symptom group could be a good candidate for subsequent genetic research.

Cannabidiol for the treatment of cannabis withdrawal syndrome: a case report.

PubMed

Crippa, J A S; Hallak, J E C; Machado-de-Sousa, J P; Queiroz, R H C; Bergamaschi, M; Chagas, M H N; Zuardi, A W

2013-04-01

  Cannabis withdrawal in heavy users is commonly followed by increased anxiety, insomnia, loss of appetite, migraine, irritability, restlessness and other physical and psychological signs. Tolerance to cannabis and cannabis withdrawal symptoms are believed to be the result of the desensitization of CB1 receptors by THC.   This report describes the case of a 19-year-old woman with cannabis withdrawal syndrome treated with cannabidiol (CBD) for 10 days. Daily symptom assessments demonstrated the absence of significant withdrawal, anxiety and dissociative symptoms during the treatment.   CBD can be effective for the treatment of cannabis withdrawal syndrome. © 2012 Blackwell Publishing Ltd.

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.

Bone mass, depressive and anxiety symptoms in adolescent girls: Variation by smoking and alcohol use

PubMed Central

Dorn, L.D.; Pabst, S.; Sontag, L.M.; Kalkwarf, H.; Hillman, J.B.; Susman, E.J.

2011-01-01

PURPOSE The purpose of the study was to examine (a) the association between depressive and anxiety symptoms with bone health, (b) the association of smoking or alcohol use with bone health, and, in turn, (c) whether the association between depressive and anxiety symptoms with bone health varied by smoking or alcohol use individually or by combined use. Bone health included total body bone mineral content (TB BMC) and bone mineral density (BMD) of the lumbar spine, total hip, and femoral neck. Previous literature has not examined these issues in adolescence, a time when more than 50% of bone mass is accrued. METHODS An observational study enrolled 262 healthy adolescent girls by age cohort (11, 13, 15, and 17 years). Participants completed questionnaires and interviews on substance use, depressive symptoms, and anxiety. BMC and BMD were measured by dual energy x-ray absorptiometry. RESULTS Higher depressive symptoms were associated with lower TB BMC and BMD (total hip, femoral neck). Those with the lowest level of smoking had higher BMD of the hip and femoral neck whereas no differences were noted by alcohol use. Regular users of both cigarettes and alcohol demonstrated a stronger negative association between depressive symptoms and TB BMC compared with non-users/experimental users and regular alcohol users. Findings were parallel for anxiety symptoms. CONCLUSION Depressive and anxiety symptoms may negatively influence bone health in adolescent girls. Consideration of multiple substances, rather than cigarettes or alcohol separately, may be particularly informative with respect to the association of depression with bone health. PMID:22018564

Psychiatric Symptoms and Alcohol Use in Community Violence by Persons With a Psychotic Disorder or Depression

PubMed Central

Yang, Suzanne; Mulvey, Edward P.; Loughran, Thomas A.; Hanusa, Barbara H.

2013-01-01

Objective Prior studies have shown a significant but modest association between mental disorders and violence and an increased risk in the presence of co-occurring substance use disorders. Categorical diagnoses, however, have limited utility when assessing dynamic risk state over time. This study used data from the MacArthur Violence Risk Assessment Study to examine the relationship of symptom levels and alcohol use to violence in repeated observations within two diagnostic groups. Methods Participants with a primary categorical diagnosis of depression (N=386) or a psychotic disorder (N=201) were identified. Subscale scores for affective or positive symptoms from the Brief Psychiatric Rating Scale and self-reported alcohol consumption were tested in panel logistic models over five ten-week intervals for their concurrent and lagged relationship to violence. An interaction term between each type of symptom and alcohol use was also tested. Results In models including the amount of alcohol consumed and symptom levels, a high level of affective symptoms was associated with violence during the next follow-up period only for participants with depression. There was a significant interaction between alcohol use and affective symptoms for participants with depression. Conclusions The relationship of symptoms and alcohol use to community violence should be considered in the context of the individual’s primary diagnosis. Further characterization of interactions between symptoms and substance use in relation to violent behavior may allow for more effective assessment of risk state and interventions for violence prevention. PMID:22388531

Alcohol Use, Depressive Symptoms, and Impulsivity as Risk Factors for Suicide Proneness among College Students

PubMed Central

Dvorak, Robert D.; Lamis, Dorian A.; Malone, Patrick S.

2013-01-01

BACKGROUND Alcohol use, depression, and suicide are significant public health problems, particularly among college students. Impulsivity is associated with all of these factors. Additionally, impulsivity increases the effects of negative mood and alcohol use on maladaptive behavior. METHODS The current cross-sectional study examined the association between the four-factor model of impulsivity (urgency, (lack of) perseverance, (lack of) premeditation, and sensation seeking), depressive symptoms, and alcohol use as predictors of suicide proneness among college students. Participants (n =1100) completed online assessments of demographics, impulsivity, depressive symptoms, and suicide proneness. RESULTS All predictors were positively related to suicide proneness. The relation between depressive symptoms and suicide proneness was moderated by (lack of) perseverance, alcohol use, and joint interactions of urgency × alcohol use and sensation seeking × alcohol use. Despite some paradoxical findings regarding the depressive symptoms-suicide proneness relation when only one risk factor was elevated, the average level of suicide proneness increased as risk factors increased. LIMITATIONS This cross-sectional self-report data comes from a non-clinical sample of college students from a homogeneous background, limiting generalizability and causal predictions. CONCLUSIONS Overall, these findings indicate that the association between depressive symptoms and suicide proneness varies considerably by different facets of impulsivity and alcohol use. The results suggest that clinical risk-assessments should weigh two forms of impulsivity (urgency and sensation seeking) as particularly vital in the presence of heavy alcohol use. These findings highlight the importance of considering and exploring moderators of the mood-suicide relationship. PMID:23474093

Alcohol use, depressive symptoms, and impulsivity as risk factors for suicide proneness among college students.

PubMed

Dvorak, Robert D; Lamis, Dorian A; Malone, Patrick S

2013-07-01

Alcohol use, depression, and suicide are significant public health problems, particularly among college students. Impulsivity is associated with all of these factors. Additionally, impulsivity increases the effects of negative mood and alcohol use on maladaptive behavior. The current cross-sectional study examined the association between the four-factor model of impulsivity (urgency, (lack of) perseverance, (lack of) premeditation, and sensation seeking), depressive symptoms, and alcohol use as predictors of suicide proneness among college students. Participants (n=1100) completed online assessments of demographics, impulsivity, depressive symptoms, and suicide proneness. All predictors were positively related to suicide proneness. The relation between depressive symptoms and suicide proneness was moderated by (lack of) perseverance, alcohol use, and joint interactions of urgency×alcohol use and sensation seeking×alcohol use. Despite some paradoxical findings regarding the depressive symptoms-suicide proneness relation when only one risk factor was elevated, the average level of suicide proneness increased as risk factors increased. This cross-sectional self-report data comes from a non-clinical sample of college students from a homogeneous background, limiting generalizability and causal predictions. Overall, these findings indicate that the association between depressive symptoms and suicide proneness varies considerably by different facets of impulsivity and alcohol use. The results suggest that clinical risk-assessments should weigh two forms of impulsivity (urgency and sensation seeking) as particularly vital in the presence of heavy alcohol use. These findings highlight the importance of considering and exploring moderators of the mood-suicide relationship. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

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.

Anxiety and depression symptoms and alcohol use among adolescents - a cross sectional study of Norwegian secondary school students.

PubMed

Johannessen, Espen Lund; Andersson, Helle Wessel; Bjørngaard, Johan Håkon; Pape, Kristine

2017-05-23

We investigated the associations between symptoms of anxiety and depression and alcohol drinking behavior among adolescents, by focusing on the importance of symptom load, as well as gender differences. Data was derived from a cross-sectional school based survey among adolescents in upper secondary schools in Norway. Among other variables adolescents reported on symptoms of anxiety and depression, time of onset and extent of alcohol use. The sample consisted of 6238 adolescents aged 16-18 years. We estimated prevalence of alcohol drinking behaviors in relation to severity of symptoms of anxiety and depression. Higher levels of depression symptoms were associated with earlier onset of alcohol use, more frequent consumption and intoxications. The associations between anxiety and depression symptoms and early drinking onset were stronger for girls than for boys. Higher levels of anxiety symptoms were only associated with alcohol consumption among girls. Boys and girls with depressive symptoms and girls with anxiety symptoms are more likely to have unhealthy patterns of alcohol drinking. Preventive strategies at all levels could possibly profit from a common approach to mental health and alcohol use, in particular for girls in mid-adolescence.

Associations between access to alcohol outlets and alcohol intake and depressive symptoms in women from socioeconomically disadvantaged neighbourhoods in Australia.

PubMed

Lamb, Karen E; Thornton, Lukar E; Teychenne, Megan; Milte, Catherine; Cerin, Ester; Ball, Kylie

2017-01-17

This study examined associations between alcohol outlet access and alcohol intake, depressive symptoms score and risk of depression among women residing in disadvantaged neighbourhoods in Victoria, Australia. Data on depressive symptoms, alcohol intake and socio-demographic characteristics were obtained from a sample of 995 adult women from Victoria, Australia who were surveyed as part of the Resilience in Eating and Activity Despite Inequality (READI) study. The location of all licensed alcohol outlets in Victoria was obtained from the Victorian Commission for Gambling and Liquor Regulation. Participant and alcohol outlet addresses were geocoded to calculate individual alcohol outlet access, defined as the number of outlets (all and by sub-type) within 0.4 km and 3 km of participants' homes. Separate regression models with clustered standard errors were fitted to examine associations between access and alcohol intake according to national recommended limits for short- and long-term harm, frequency of consumption above long-term harm guidelines, depressive symptoms score and risk of depression. Odds of consumption within short-term harm guidelines (≤4 drinks on any day) decreased with increasing access within 3 km, irrespective of outlet type. Typically, there was no evidence to support associations between access and consumption above long-term harm guidelines (>2 drinks on any day) unless considering frequency of consumption at this level where results showed decreased odds of 'don't drink' versus frequently drinking above long-term harm guidelines (i.e., >2 drinks at least once per week) with increasing access at either distance. Although there was no evidence of an association between any of the alcohol outlet access measures and depressive symptoms score, odds of being at risk of depression decreased with increasing access within 3 km. This study found some evidence to support an association between increasing alcohol outlet densities of all types and

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.

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

Network approach to the symptom-level association between alcohol use disorder and posttraumatic stress disorder.

PubMed

Afzali, Mohammad H; Sunderland, Matthew; Batterham, Philip J; Carragher, Natacha; Calear, Alison; Slade, Tim

2017-03-01

The high prevalence of alcohol use disorder among individuals with a history of trauma and posttraumatic stress disorder is well documented. The current study applied network analysis to map the structure of symptom associations between these disorders. Data come from a community sample of 449 Australian adults with a history of trauma and alcohol consumption during the last 12 months. Data analysis consisted of the construction of the comorbidity network of PTSD/AUD symptoms, identification of the bridging symptoms, computation of the centrality measures, and evaluation of the robustness of the results. Results highlighted two main symptom clusters, corresponding to two disorders, and that only nine edges connected the two clusters. Bridging symptoms connecting the two clusters were: alcohol use in dangerous situations, physical or mental health problems as a result of alcohol use, loss of interest or reduced social activities, and reckless/self-destructive behaviour. Identification of both central symptoms, because of their key role in the constellation and strong associations with majority of symptoms, and bridge symptoms, because of their mediating role between two disorders, has some implications in terms of self-medication and risk-taking/self-regulation theories of comorbidity and provides a number of clinical implications, which warrants further exploration within clinical samples.

Craving as a DSM-5 Symptom of Alcohol Use Disorder in Non-Treatment Seekers.

PubMed

Hartwell, Emily E; Ray, Lara A

2018-05-01

DSM-5 has added craving as a new criterion and changed the diagnostic structure of alcohol use disorder (AUD). Though craving has long been a target of intervention, less is known about the impact this addition will have on prevalence and factor structure of AUD, particularly in non-treatment seeker with alcohol problems. Non-treatment seeking individuals reporting alcohol-related problems (N = 296) completed a structured clinical interview and the Penn Alcohol Craving Scale (PACS). PACS scores greater than 20 were considered to meet diagnostic criteria for the alcohol craving symptom. This study examined DSM-IV to DSM-5 diagnostic conversion and conducted an exploratory factor analysis to test the factor structure of the DSM-5 symptoms, including craving. The mean PACS score was 13.1 and alcohol craving was strongly correlated with other measures of alcohol use. Using the proposed cut-off score of PACS > 20, 46 participants (16.2%) met criteria for alcohol craving. Craving loaded moderately (0.47) onto the retained DSM symptoms and produced a unidimensional factor structure. The majority of participants who met for a DSM-IV AUD also met for a DSM-5 AUD (98.8%). Craving prevalence using the PACS was relatively low compared to the remaining 10 DSM-5 symptoms, possibly due to the non-treatment seeking nature of the sample. Conversion of DSM-IV to DSM-5 in this sample led to a small increase in overall AUD prevalence. Craving loaded well onto a single factor structure for AUD.

A test of the stress-buffering model of social support in smoking cessation: is the relationship between social support and time to relapse mediated by reduced withdrawal symptoms?

PubMed

Creswell, Kasey G; Cheng, Yu; Levine, Michele D

2015-05-01

Social support has been linked to quitting smoking, but the mechanisms by which social support affects cessation are poorly understood. The current study tested a stress-buffering model of social support, which posits that social support protects or "buffers" individuals from stress related to quitting smoking. We hypothesized that social support would be negatively associated with risk of relapse, and that this effect would be mediated by reduced withdrawal and depressive symptoms (i.e., cessation-related stress) over time. Further, we predicted that trait neuroticism would moderate this mediational effect, such that individuals high in negative affectivity would show the greatest stress-buffering effects of social support. Participants were weight-concerned women (n = 349) ages 18-65 enrolled in a randomized, double-blind, placebo-controlled smoking cessation trial of bupropion and cognitive behavioral therapy. Social support was assessed at baseline, and biochemically-verified abstinence, withdrawal-related symptoms, and depressive symptoms were assessed at 1-, 3-, 6-, and 12-months follow-up. Social support was negatively related to risk of relapse in survival models and negatively related to withdrawal symptoms and depression in mixed effects models. These relationships held after controlling for the effects of pre-quit day negative affect and depression symptoms, assignment to treatment condition, and number of cigarettes smoked per day. A temporal mediation model showed that the effect of social support on risk of relapse was mediated by reductions in withdrawal symptoms over time but not by depression over time. Contrary to hypotheses, we did not find that neuroticism moderated this mediation effect. Increased social support may buffer women from the harmful effects of cessation-related withdrawal symptoms, which in turn improve cessation outcomes. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and

A Test of the Stress-Buffering Model of Social Support in Smoking Cessation: Is the Relationship Between Social Support and Time to Relapse Mediated by Reduced Withdrawal Symptoms?

PubMed Central

Cheng, Yu; Levine, Michele D.

2015-01-01

Introduction: Social support has been linked to quitting smoking, but the mechanisms by which social support affects cessation are poorly understood. The current study tested a stress-buffering model of social support, which posits that social support protects or “buffers” individuals from stress related to quitting smoking. We hypothesized that social support would be negatively associated with risk of relapse, and that this effect would be mediated by reduced withdrawal and depressive symptoms (i.e., cessation-related stress) over time. Further, we predicted that trait neuroticism would moderate this mediational effect, such that individuals high in negative affectivity would show the greatest stress-buffering effects of social support. Methods: Participants were weight-concerned women (n = 349) ages 18–65 enrolled in a randomized, double-blind, placebo-controlled smoking cessation trial of bupropion and cognitive behavioral therapy. Social support was assessed at baseline, and biochemically-verified abstinence, withdrawal-related symptoms, and depressive symptoms were assessed at 1-, 3-, 6-, and 12-months follow-up. Results: Social support was negatively related to risk of relapse in survival models and negatively related to withdrawal symptoms and depression in mixed effects models. These relationships held after controlling for the effects of pre-quit day negative affect and depression symptoms, assignment to treatment condition, and number of cigarettes smoked per day. A temporal mediation model showed that the effect of social support on risk of relapse was mediated by reductions in withdrawal symptoms over time but not by depression over time. Contrary to hypotheses, we did not find that neuroticism moderated this mediation effect. Conclusions: Increased social support may buffer women from the harmful effects of cessation-related withdrawal symptoms, which in turn improve cessation outcomes. PMID:25257978

Evaluation of smokers with and without asthma in terms of smoking cessation outcome, nicotine withdrawal symptoms, and craving: Findings from a self-guided quit attempt.

PubMed

McLeish, Alison C; Farris, Samantha G; Johnson, Adrienne L; Bernstein, Jonathan A; Zvolensky, Michael J

2016-12-01

The aim of the current study was to evaluate smoking cessation outcome, nicotine withdrawal symptoms, and craving between smokers with (n=47; 46.8% male, Mage=40.0years, SD=11.7) and without (n=45; 51.1% male, Mage=37.5years, SD=11.1) asthma during a self-guided quit attempt. After completing a baseline assessment visit, participants attended study sessions on their scheduled quit day as well as follow-up visits (3days, 7days, 14days, and 28days) after their quit day. Smokers with and without asthma did not differ in abstinence rates, smoking lapse, and rate of change in urge to smoke to reduce negative affect. However, smokers with asthma demonstrated a slower rate of decline in nicotine withdrawal symptoms and craving over time. These findings suggest that smokers with asthma may benefit from specialized smoking cessation treatments to address prolonged withdrawal symptoms and craving. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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

Posttraumatic stress disorder symptoms, anxiety sensitivity, and alcohol-use motives in college students with a history of interpersonal trauma.

PubMed

Berenz, Erin C; Kevorkian, Salpi; Chowdhury, Nadia; Dick, Danielle M; Kendler, Kenneth S; Amstadter, Ananda B

2016-11-01

Posttraumatic stress disorder (PTSD) symptoms are associated with coping-motivated alcohol use in trauma-exposed samples. However, it is unclear which individuals experiencing PTSD symptoms are at greatest risk for alcohol-use problems following trauma exposure. Individuals endorsing high anxiety sensitivity, which is the fear of anxiety and related sensations, may be particularly motivated to use alcohol to cope with PTSD symptoms. In the current study, we examined the moderating role of anxiety sensitivity in the association between PTSD symptoms and coping motives in a sample of 295 young adults with a history of interpersonal trauma and current alcohol use. Participants completed measures of past 30-day alcohol consumption, trauma history, current PTSD symptoms, anxiety sensitivity, and alcohol-use motives. Results of hierarchical multiple regression analyses indicated that greater anxiety sensitivity was significantly associated with greater coping (β = .219) and conformity (β = .156) alcohol-use motives, and greater PTSD symptoms were associated with greater coping motives (β = .247), above and beyond the covariates of sex, alcohol consumption, trauma load, and noncriterion alcohol-use motives. The interaction of anxiety sensitivity and PTSD symptoms accounted for additional variance in coping motives above and beyond the main effects (β = .117), with greater PTSD symptoms being associated with greater coping motives among those high but not low in anxiety sensitivity. Assessment and treatment of PTSD symptoms and anxiety sensitivity in young adults with interpersonal trauma may be warranted as a means of decreasing alcohol-related risk in trauma-exposed young adults. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

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.

Precursors of social emotional functioning among full-term and preterm infants at 12 months: Early infant withdrawal behavior and symptoms of maternal depression.

PubMed

Moe, Vibeke; Braarud, Hanne Cecilie; Wentzel-Larsen, Tore; Slinning, Kari; Vannebo, Unni Tranaas; Guedeney, Antoine; Heimann, Mikael; Rostad, Anne Margrethe; Smith, Lars

2016-08-01

This study forms part of a longitudinal investigation of early infant social withdrawal, maternal symptoms of depression and later child social emotional functioning. The sample consisted of a group of full-term infants (N=238) and their mothers, and a group of moderately premature infants (N=64) and their mothers. At 3 months, the infants were observed with the Alarm Distress Baby Scale (ADBB) and the mothers completed the Edinburgh Postnatal Depression Scale (EPDS). At 12 months, the mothers filled out questionnaires about the infants' social emotional functioning (Infant Toddler Social Emotional Assessment and the Ages and Stages Questionnaire-Social Emotional). At 3 months, as we have previously shown, the premature infants had exhibited more withdrawal behavior and their mothers reported elevated maternal depressive symptoms as compared with the full-born group. At 12 months the mothers of the premature infants reported more child internalizing behavior. These data suggest that infant withdrawal behavior as well as maternal depressive mood may serve as sensitive indices of early risk status. Further, the results suggest that early maternal depressive symptoms are a salient predictor of later child social emotional functioning. However, neither early infant withdrawal behavior, nor gestational age, did significantly predict social emotional outcome at 12 months. It should be noted that the differences in strength of the relations between ADBB and EPDS, respectively, to the outcome at 12 months was modest. An implication of the study is that clinicians should be aware of the complex interplay between early infant withdrawal and signs of maternal postpartum depression in planning ports of entry for early intervention. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Serotonin receptor, SERT mRNA and correlations with symptoms in males with alcohol dependence and suicide.

PubMed

Thompson, P M; Cruz, D A; Olukotun, D Y; Delgado, P L

2012-09-01

This study tested the hypothesis that abnormalities in components of the serotonin (5HT) system in the prefrontal cortex are associated with suicide in alcohol-dependent subjects. Second, we assessed the relationship of lifetime impulsivity and mood symptoms with prefrontal cortex 5-HT measures. Tissue was obtained from Brodmann's areas (BA) 9 and 24 in postmortem samples of individuals who were alcohol dependent with suicide (n = 5), alcohol dependent without suicide (n = 9) and normal controls (n = 5). Serotonin receptor (5HT) and serotonin reuptake transporter (SERT) mRNA were measured. Interviews with next of kin estimated lifetime impulsivity and mood symptoms in the last week of life. Serotonin receptor 1A (5HT1A) mRNA in BA 9 was elevated in the alcohol dependence without suicide group compared with controls. In the alcohol dependence with suicide group, anxiety symptoms were associated with decreased BA 24 SERT mRNA and depressive symptoms with BA 9 5HT1A mRNA expression. In the alcohol dependent only group impulsivity is correlated with increased BA 9, and BA 24 serotonin receptor 2A mRNA. Our data suggest region-specific change, rather than global serotonin blunting is involved in alcohol dependence and suicide. It also suggests that symptoms are differentially influenced by prefrontal cortex serotonin receptor mRNA levels. © 2011 John Wiley & Sons A/S.

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.

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

Sociodemographic Characteristics of Cannabis Smokers and the Experience of Cannabis Withdrawal

PubMed Central

Copersino, Marc L.; Boyd, Susan J.; Tashkin, Donald P.; Huestis, Marilyn A.; Heishman, Stephen J.; Dermand, John C.; Simmons, Michael S.; Gorelick, David A.

2011-01-01

Background Cannabis withdrawal can be a negative reinforcer for relapse, but little is known about its association with demographic characteristics. Objectives Evaluate the association of demographic characteristics with the experience of cannabis withdrawal. Methods Retrospective self-report of a “serious” cannabis quit attempt without formal treatment in a convenience sample of 104 non-treatment-seeking, adult cannabis smokers (mean age 35 years, 52% white, 78% male) with no other current substance use disorder (except tobacco) or chronic health problems. Reasons for quitting, coping strategies to help quit, and 18 specific withdrawal symptoms were assessed by questionaire. Results Among withdrawal symptoms, only anxiety, increased sex drive, and craving showed significant associations with age, race, or sex. Women were more likely than men to report a physical withdrawal symptom (OR = 3.2, 95% CI = .99–10.4, p = .05), especially upset stomach. There were few significant demographic associations with coping strategies or reasons for quitting. Conclusions and Scientific Significance This small study suggests that there are few robust associations between demographic characteristics and cannabis withdrawal. Future studies with larger samples are needed. Attention to physical withdrawal symptoms in women may help promote abstinence. PMID:20678028

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.

A Short-Term, Multicenter, Placebo-Controlled, Randomized Withdrawal Study of a Metabotropic Glutamate 2/3 Receptor Agonist Using an Electronic Patient-Reported Outcome Device in Patients With Schizophrenia

PubMed Central

Stauffer, Virginia L.; Baygani, Simin K.; Kinon, Bruce J.; Krikke-Workel, Judith O.

2014-01-01

Abstract This 6-week, multicenter, randomized withdrawal, placebo-controlled trial sought to determine whether symptoms of physical dependence occur after abrupt cessation of pomaglumetad methionil (LY2140023 monohydrate), a metabotropic glutamate 2/3 receptor agonist, in patients with schizophrenia. Eligible outpatients, 18 to 65 years old who required a modification or initiation of antipsychotic medication received 4 weeks of pomaglumetad methionil during open-label treatment and then were randomized, double-blind, to continue pomaglumetad methionil or receive placebo for 2 weeks. The primary outcome compared results of the 3-day moving mean of the total score on the Discontinuation Symptom Checklist-Modified Rickels for pomaglumetad methionil-treated patients with those on placebo during the randomized withdrawal phase. An electronic patient-reported outcome (ePRO) device was used daily to record these results. During the withdrawal phase, 103 patients were randomized, and 98 patients completed the trial. There was no statistically significant evidence of withdrawal symptoms associated with placebo compared with pomaglumetad methionil continuation as measured by Discontinuation Symptom Checklist-Modified Rickels (P = 0.170). The results are supported by secondary analyses with the clinician-rated, Clinical Institute Withdrawal Assessment of Alcohol Scale Revised, which showed no statistically significant differences between treatment groups. Using the ePRO device, 82.5% of the patients achieved 75% to 100% of compliance. No discontinuations due to worsening of schizophrenia, serious adverse events, deaths, or seizures were reported during either phase of the study. These findings suggest that there is no evidence of withdrawal symptoms associated with the abrupt discontinuation of pomaglumetad methionil and that an ePRO device can be successfully used in a multicenter schizophrenia trial. PMID:25006819

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.

PTSD symptom presentation among people with alcohol and drug use disorders: Comparisons by substance of abuse.

PubMed

Dworkin, Emily R; Wanklyn, Sonya; Stasiewicz, Paul R; Coffey, Scott F

2018-01-01

Posttraumatic stress disorder (PTSD) and substance use disorders (SUDs) commonly co-occur, and there is some evidence to suggest that PTSD symptom clusters are differentially related to various substances of abuse. However, few studies to date have compared PTSD symptom patterns across people with different types of SUDs, and fewer still have accounted for the presence of comorbidity across types of SUDs in understanding symptom patterns. Thus, in the current study, we use a treatment-seeking sample of people with elevated symptoms of PTSD and problem alcohol use to explore differential associations between past-year SUDs with active use and PTSD symptoms, while accounting for the presence of multiple SUDs. When comparing alcohol and drug use disorders, avoidance symptoms were elevated in those with alcohol use disorder, and hyperarousal symptoms were elevated in those who had a drug use disorder. In the subsample with alcohol use disorder, hyperarousal symptoms were elevated in people with co-occurring cocaine use disorders and numbing symptoms were elevated in people with co-occurring sedative/hypnotic/anxiolytic use disorder. These findings provide evidence for different symptom cluster patterns between PTSD and various types of SUDs and highlight the importance of examining the functional relationship between specific substances of abuse when understanding the interplay between PTSD and SUDs. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

Interactions Between Internalizing Symptoms and Urgency in the Prediction of Alcohol Use and Expectancies Among Low-Income, Minority Early Adolescents

PubMed Central

Marmorstein, Naomi R.

2015-01-01

This study examined whether urgency, a disposition to rash action under conditions of strong emotion, moderates associations between internalizing symptoms and alcohol use and related expectancies. Data from the Camden Youth Development Study, a longitudinal, community-based study of early adolescents (N = 144, mean age at intake = 11.9 years; 65% Hispanic, 30% African-American; 50% male), were used. Self-report questionnaire measures of depressive symptoms, social and generalized anxiety symptoms, urgency, alcohol use, and alcohol expectancies were used. Mixed models were used to examine the effects of internalizing symptoms, urgency, and their interaction on alcohol use and expectancy trajectories over time. Depressive symptoms interacted with urgency such that youth with high levels of both tended to have elevated levels of global positive alcohol expectancies. Social anxiety symptoms interacted with urgency to be associated with increasing levels of social behavior alcohol expectancies such that youth with high levels of both tended to experience particular increases in these expectancies over time. Generalized anxiety was not found to be associated with alcohol-related constructs. Therefore, high levels of urgency combine with depressive and social anxiety symptoms to be associated with particularly increased risk for alcohol expectancies that are associated with later alcohol use and problems, indicating particular risk for youth with these combinations of personality traits and psychopathology symptoms. PMID:27512337

PTSD Symptoms, Emotion Dysregulation, and Alcohol-Related Consequences Among College Students With a Trauma History.

PubMed

Tripp, Jessica C; McDevitt-Murphy, Meghan E; Avery, Megan L; Bracken, Katherine L

2015-01-01

Posttraumatic stress disorder (PTSD), alcohol use, and alcohol-related consequences have been linked to emotion dysregulation. Sex differences exist in both emotion regulation dimensions and alcohol use patterns. This investigation examined facets of emotion dysregulation as potential mediators of the relationship between PTSD symptoms and alcohol-related consequences and whether differences may exist across sexes. Participants were 240 college students with a trauma history who reported using alcohol within the past three months and completed measures of PTSD symptoms, emotion dysregulation, alcohol consumption, alcohol-related consequences, and negative affect. The six facets of emotion dysregulation were examined as mediators of the relationship between PTSD symptoms and alcohol-related consequences in the full sample and by sex. There were differences in sexes on several variables, with women reporting higher PTSD scores and lack of emotional awareness. Men reported significantly more drinks per week in a typical week and a heavy week. There were significant associations between the variables for the full sample, with PTSD showing associations with five facets of emotion dysregulation subscales: impulse control difficulties when upset, difficulties engaging in goal-directed behavior, nonacceptance of emotional responses, lack of emotional clarity, and limited access to emotion regulation strategies. Alcohol-related consequences were associated with four aspects of emotion dysregulation: impulse control difficulties when upset, difficulties engaging in goal-directed behavior, nonacceptance of emotional responses, and limited access to emotion regulation strategies. Two aspects of emotion regulation, impulse control difficulties and difficulties engaging in goal directed behavior, mediated the relationship between PTSD symptoms and alcohol-related consequences in the full sample, even after adjusting for the effects of negative affect. When examined separately by

Associations of Drug Use, Violence, and Depressive Symptoms with Sexual Risk Behaviors Among Women with Alcohol Misuse.

PubMed

Lee, Kristen; Hutton, Heidi E; Lesko, Catherine R; Monroe, Anne K; Alvanzo, Anika; McCaul, Mary E; Chander, Geetanjali

2018-05-18

Alcohol misuse is associated with increased human immunodeficiency virus sexual risk behaviors by women. Drug use, intimate partner violence (IPV), and depressive symptoms frequently co-occur, are well-recognized alcohol misuse comorbidities, and may interact to increase risk behaviors. Using a syndemic framework we examined associations between drug use, IPV, and depressive symptoms and sexual risk behaviors by 400 women with alcohol misuse attending an urban sexually transmitted infections clinic. Participants completed computer-assisted interviews querying drug use, IPV, and depressive symptoms and sexual risk behavior outcomes-unprotected sex under the influence of alcohol, sex for drugs/money, and number of lifetime sexual partners. We used multivariable analysis to estimate prevalence ratios (PR) for independent and joint associations between drug use, IPV, and depressive symptoms and our outcomes. To investigate synergy between risk factors we calculated the relative excess prevalence owing to interaction for all variable combinations. In multivariable analysis, drug use, IPV, and depressive symptoms alone and in combination were associated with higher prevalence/count of risk behaviors compared with women with alcohol misuse alone. The greatest prevalence/count occurred when all three were present (unprotected sex under the influence of alcohol [PR, 2.6; 95% confidence interval, 1.3-4.9]), sex for money or drugs [PR, 2.6; 95% confidence interval, 1.7-4.2], and number of lifetime partners [PR, 3.2; 95% confidence interval, 1.9-5.2]). Drug use, IPV, and depressive symptoms did not interact synergistically to increase sexual risk behavior prevalence. A higher prevalence of sexual risk behaviors by women with alcohol misuse combined with drug use, IPV, and depressive symptoms supports the need for alcohol interventions addressing these additional comorbidities. Copyright © 2018 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Nebivolol withdrawal results in blood pressure returning toward pretreatment levels, but without rebound symptoms: phase IV randomized trial.

PubMed

Lewin, Andrew; Lasseter, Kenneth C; Dong, Fang; Whalen, John C

2012-01-01

Rapid withdrawal of antihypertensive drugs may lead to blood pressure (BP) increase above pretreatment values or symptoms such as palpitations, chest pain, and tremor. This phase IV trial assessed the consequences of abrupt and stepwise withdrawal of nebivolol, a β(1)-selective blocker, in individuals with stage I-II hypertension. After a 4- to 5-week placebo washout phase and 12-week single-blind nebivolol treatment (10-40 mg/day, titrated based on BP response), participants achieving BP control (systolic BP [SBP]/diastolic BP [DBP] <140/90 mm Hg) or response (SBP decrease ≥10 mm Hg or DBP decrease ≥5 mm Hg) entered a 4-week, randomized, double-blind phase of continued nebivolol treatment (n = 102) or withdrawal to placebo (n = 105). Primary and secondary efficacy measures were changes in mean sitting DBP and SBP, respectively, analyzed using an analysis of covariance model. Safety and tolerability were also assessed. In the withdrawal phase, nebivolol and placebo groups demonstrated mean DBP increases of 1.8 and 7.7 mm Hg, respectively (P < .001), and SBP increases of 3.5 and 7.6 mm Hg (P = .011). Twenty-three (22.5%) nebivolol-treated and 18 (17.1%) placebo-treated participants experienced a treatment-emergent adverse event. No adverse events associated with β-blocker withdrawal and considered causally related to nebivolol were reported. Nebivolol withdrawal resulted in a mean BP increase near pretreatment levels and was not associated with rebound hypertension. Copyright © 2012 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

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...

Activation of serotonin 5-HT2C receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in morphine-dependent mice

PubMed Central

Zhang, Gongliang; Wu, Xian; Zhang, Yong-Mei; Liu, Huan; Jiang, Qin; Pang, Gang; Tao, Xinrong; Dong, Liuyi; Stackman, Robert W.

2015-01-01

Opioid abuse and dependence have evolved into an international epidemic as a significant clinical and social problem with devastating consequences. Repeated exposure to the opioid, for example morphine, can induce profound, long-lasting behavioral sensitization and physical dependence, which are thought to reflect neuroplasticity in neural circuitry. Central serotonin (5-HT) neurotransmission participates in the development of dependence on and the expression of withdrawal from morphine. Serotonin 5-HT2C receptor (5-HT2CR) agonists suppress psychostimulant nicotine or cocaine-induced behavioral sensitization and drug-seeking behavior; however, the impact of 5-HT2CR agonists on behaviors relevant to opioid abuse and dependence has not been reported. In the present study, the effects of 5-HT2CR activation on the behavioral sensitization and naloxone-precipitated withdrawal symptoms were examined in mice underwent repeated exposure to morphine. Male mice received morphine (10 mg/kg, s.c.) to develop behavioral sensitization. Lorcaserin, a 5-HT2CR agonist, prevented the induction and expression, but not the development, of morphine-induced behavioral sensitization. Another cohort of mice received increasing doses of morphine over a 7-day period to induce morphine-dependence. Pretreatment of lorcaserin, or the positive control clonidine (an alpha 2-adrenoceptor agonist), ameliorated the naloxone-precipitated withdrawal symptoms. SB 242084, a selective 5-HT2CR antagonist, prevented the lorcaserin-mediated suppression of behavioral sensitization and withdrawal. Chronic morphine treatment was associated with an increase in the expression of 5-HT2CR protein in the ventral tegmental area, locus coeruleus and nucleus accumbens. These findings suggest that 5-HT2CR can modulate behavioral sensitization and withdrawal in morphine-dependent mice, and the activation of 5-HT2CR may represent a new avenue for the treatment of opioid addiction. PMID:26432939

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...

Patterns of change in withdrawal symptoms, desire to smoke, reward motivation and response inhibition across 3 months of smoking abstinence.

PubMed

Dawkins, Lynne; Powell, Jane H; Pickering, Alan; Powell, John; West, Robert

2009-05-01

We have demonstrated previously that acute smoking abstinence is associated with lowered reward motivation and impaired response inhibition. This prospective study explores whether these impairments, along with withdrawal-related symptoms, recover over 3 months of sustained abstinence. Participants completed a 12-hour abstinent baseline assessment and were then allocated randomly to quit unaided or continue smoking. All were re-tested after 7 days, 1 month and 3 months. Successful quitters' scores were compared with those of continuing smokers, who were tested after ad libitum smoking. Goldsmiths, University of London. A total of 33 smokers who maintained abstinence to 3 months, and 31 continuing smokers. Indices demonstrated previously in this cohort of smokers to be sensitive to the effect of nicotine versus acute abstinence: reward motivation [Snaith-Hamilton pleasure scale (SHAPS), Card Arranging Reward Responsivity Objective Test (CARROT), Stroop], tasks of response inhibition [anti-saccade task; Continuous Performance Task (CPT)], clinical indices of mood [Hospital Anxiety and Depression Scale (HADS)], withdrawal symptoms [Mood and Physical Symptoms Scale (MPSS)] and desire to smoke. SHAPS anhedonia and reward responsivity (CARROT) showed significant improvement and plateaued after a month of abstinence, not differing from the scores of continuing smokers tested in a satiated state. Mood, other withdrawal symptoms and desire to smoke all declined from acute abstinence to 1 month of cessation and were equivalent to, or lower than, the levels reported by continuing, satiated smokers. Neither group showed a change in CPT errors over time while continuing smokers, but not abstainers, showed improved accuracy on the anti-saccade task at 3 months. Appetitive processes and related affective states appear to improve in smokers who remain nicotine-free for 3 months, whereas response inhibition does not. Although in need of replication, the results suggest tentatively

Non-alcoholic fatty liver disease is associated with high prevalence of gastro-oesophageal reflux symptoms.

PubMed

Miele, Luca; Cammarota, Giovanni; Vero, Vittoria; Racco, Simona; Cefalo, Consuelo; Marrone, Giuseppe; Pompili, Maurizio; Rapaccini, Gianlodovico; Bianco, Alessandro; Landolfi, Raffaele; Gasbarrini, Antonio; Grieco, Antonio

2012-12-01

Gastro-oesophageal reflux symptoms are usually reported by patients with obesity and metabolic syndrome. Aim of this study was to assess the prevalence and clinical characteristics of gastro-oesophageal reflux symptoms in subjects with non-alcoholic fatty liver disease. Cross-sectional, case-control study of 185 consecutive patients with non-alcoholic fatty liver disease and an age- and sex-matched control group of 112 healthy volunteers. Participants were interviewed with the aid of a previously validated questionnaire to assess lifestyle and reflux symptoms in the 3 months preceding enrolment. Odds ratios were determined before and after adjustment for body mass index, increased waist circumference, physical activity, metabolic syndrome and proton pump inhibitors and/or antiacid medication. The prevalence of heartburn and/or regurgitation and of at least one of gastro-oesophageal reflux symptoms was significantly higher in the non-alcoholic fatty liver disease group. Non-alcoholic fatty liver disease subjects were associated to higher prevalence of heartburn (adjusted odds ratios: 2.17, 95% confidence intervals: 1.16-4.04), regurgitation (adjusted odds ratios: 2.61, 95% confidence intervals: 1.24-5.48) and belching (adjusted odds ratios: 2.01, 95% confidence intervals: 1.12-3.59) and had higher prevalence of at least one GER symptom (adjusted odds ratios: 3.34, 95% confidence intervals: 1.76-6.36). Non-alcoholic fatty liver disease is associated with a higher prevalence of gastro-oesophageal reflux symptoms. Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

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.

Mechanisms of Behavior Change in Alcoholics Anonymous: Does AA lead to better alcohol use outcomes by reducing depression symptoms?

PubMed Central

Kelly, John F.; Stout, Robert L.; Magill, Molly; Tonigan, J. Scott; Pagano, Maria E.

2009-01-01

Rationale Indices of negative affect, such as depression, have been implicated in stress-induced pathways to alcohol relapse. Empirically-supported continuing care resources, such as Alcoholics Anonymous (AA), emphasize reducing negative affect to reduce relapse risk, but little research has been conducted to examine putative affective mechanisms of AA’s effects. Method Using lagged, controlled, hierarchical linear modeling and mediational analyses this study investigated whether AA participation mobilized changes in depression symptoms and whether such changes explained subsequent reductions in alcohol use. Alcohol dependent adults (N = 1,706), receiving treatment as part of a clinical trial, were assessed at intake, 3, 6, 9, 12, and 15 months. Results Findings revealed elevated levels of depression compared to the general population, which decreased during treatment and then remained stable over follow-up. Greater AA attendance was associated with better subsequent alcohol use outcomes and decreased depression. Greater depression was associated with heavier and more frequent drinking. Lagged, mediation analyses revealed that the effects of AA on alcohol use was partially mediated by reductions in depression symptoms. However, this salutary effect on depression itself appeared to be explained by AA’s proximal effect on reducing concurrent drinking. Conclusions AA attendance was both concurrently and predictively associated with improved alcohol outcomes. Although AA attendance was additionally associated with subsequent improvements in depression, it did not predict such improvements over and above concurrent alcohol use. AA appears to lead both to improvements in alcohol use and psychological and emotional well-being, which, in turn, may reinforce further abstinence and recovery-related change. PMID:20102345

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

Posterior reversible encephalopathy syndrome in chronic alcoholism with acute psychiatric symptoms.

PubMed

Kimura, Ryo; Yanagida, Makoto; Kugo, Aki; Taguchi, Satoki; Matsunaga, Hidenori

2010-01-01

To highlight the association between posterior reversible encephalopathy syndrome (PRES) and chronic alcoholism. We present a case report, a review of the literature and a discussion. We report on the case of a 51-year-old man with chronic alcoholism, who suddenly developed visual disturbance and confusion. Magnetic resonance imaging (MRI) on admission demonstrated abnormal findings. However, clinical symptoms and imaging promptly improved, indicating the diagnosis of PRES. PRES should be considered when making a diagnosis for disturbed consciousness in alcoholic patients. Copyright 2010 Elsevier Inc. All rights reserved.

Is Homeopathy Effective for Hot Flashes and Other Estrogen-Withdrawal Symptoms in Breast Cancer Survivors? A Preliminary Randomized Controlled Trial

DTIC Science & Technology

2003-04-01

homeopathy may be effective in improving hot flashes and quality of life in breast cancer survivors with symptoms of estrogen withdrawal. Methods- A...scores improved significantly in both homeopathy groups compared to placebo. Results of this study suggest that a larger study should be done.

Tobacco Withdrawal Components and Their Relations with Cessation Success

PubMed Central

Piper, Megan E.; Schlam, Tanya R.; Cook, Jessica W.; Sheffer, Megan A.; Smith, Stevens S.; Loh, Wei-Yin; Bolt, Daniel M.; Kim, Su-Young; Kaye, Jesse T.; Hefner, Kathryn R.; Baker, Timothy B.

2011-01-01

Rationale Tobacco withdrawal is a key factor in smoking relapse, but important questions about the withdrawal phenomenon remain. Objectives This research was intended to provide information about two core components of withdrawal (negative affect and craving): 1) how various withdrawal symptom profile dimensions (e.g., mean level, volatility, extreme values) differ between negative affect and craving; and 2) how these dimensions relate to cessation outcome. Methods Adult smokers (N=1504) in a double-blind randomized placebo-controlled smoking cessation trial provided real-time withdrawal symptom data four times per day for 4 weeks (2 weeks pre-quit and 2 weeks post-quit) via palmtop computers. Cessation outcome was biochemically confirmed 8-week point-prevalence abstinence. Results Examination of craving and negative affect dimensions following a cessation attempt revealed that craving symptoms differed from negative affect symptoms, with higher means, greater variability, and a greater incidence of extreme peaks. Regression analyses revealed that abstinence was associated with lower mean levels of both craving and negative affect and fewer incidences of extreme craving peaks. In a multivariate model, the increase in mean craving and negative affect scores each uniquely predicted relapse. Conclusions Real-time reports revealed different patterns of abstinence-related negative affect and craving and that dimensions of both predict cessation outcome, suggesting that negative affect and craving dimensions each has motivational significance. This underscores the complexity of withdrawal as a determinant of relapse and the need to measure its distinct components and dimensions. PMID:21416234

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.

PTSD symptoms and pain in Canadian military veterans: the mediating roles of anxiety, depression, and alcohol use.

PubMed

Irwin, Kara C; Konnert, Candace; Wong, May; O'Neill, Thomas A

2014-04-01

Symptoms of posttraumatic stress disorder (PTSD) and pain are often comorbid among veterans. The purpose of this study was to investigate to what extent symptoms of anxiety, depression, and alcohol use mediated the relationship between PTSD symptoms and pain among 113 treated male Canadian veterans. Measures of PTSD, pain, anxiety symptoms, depression symptoms, and alcohol use were collected as part of the initial assessment. The bootstrapped resampling analyses were consistent with the hypothesis of mediation for anxiety and depression, but not alcohol use. The confidence intervals did not include zero and the indirect effect of PTSD on pain through anxiety was .04, CI [.03, .07]. The indirect effect of PTSD on pain through depression was .04, CI [.02, .07]. These findings suggest that PTSD and pain symptoms among veterans may be related through the underlying symptoms of anxiety and depression, thus emphasizing the importance of targeting anxiety and depression symptoms when treating comorbid PTSD and pain patients. © 2014 International Society for Traumatic Stress Studies.

A genome wide association study of alcohol dependence symptom counts in extended pedigrees identifies C15orf53

PubMed Central

Wang, Jen-Chyong; Foroud, Tatiana; Hinrichs, Anthony L; Le, Nhung XH; Bertelsen, Sarah; Budde, John P; Harari, Oscar; Koller, Daniel L; Wetherill, Leah; Agrawal, Arpana; Almasy, Laura; Brooks, Andrew I; Bucholz, Kathleen; Dick, Danielle; Hesselbrock, Victor; Johnson, Eric O; Kang, Sun; Kapoor, Manav; Kramer, John; Kuperman, Samuel; Madden, Pamela AF; Manz, Niklas; Martin, Nicholas G; McClintick, Jeanette N; Montgomery, Grant W; Nurnberger, John I; Rangaswamy, Madhavi; Rice, John; Schuckit, Marc; Tischfield, Jay A; Whitfield, John B; Xuei, Xiaoling; Porjesz, Bernice; Heath, Andrew C; Edenberg, Howard J; Bierut, Laura J; Goate, Alison M

2013-01-01

Several studies have identified genes associated with alcohol use disorders, but the variation in each of these genes explains only a small portion of the genetic vulnerability. The goal of the present study was to perform a genome-wide association study (GWAS) in extended families from the Collaborative Study on the Genetics of Alcoholism (COGA) to identify novel genes affecting risk for alcohol dependence. To maximize the power of the extended family design we used a quantitative endophenotype, measured in all individuals: number of alcohol dependence symptoms endorsed (symptom count). Secondary analyses were performed to determine if the single nucleotide polymorphisms (SNPs) associated with symptom count were also associated with the dichotomous phenotype, DSM-IV alcohol dependence. This family-based GWAS identified SNPs in C15orf53 that are strongly associated with DSM-IV alcohol (p=4.5×10−8, inflation corrected p=9.4×10−7). Results with DSM-IV alcohol dependence in the regions of interest support our findings with symptom count, though the associations were less significant. Attempted replications of the most promising association results were conducted in two independent samples: non-overlapping subjects from the Study of Addiction: Genes and Environment (SAGE) and the Australian twin-family study of alcohol use disorders (OZALC). Nominal association of C15orf53 with symptom count was observed in SAGE. The variant that showed strongest association with symptom count, rs12912251 and its highly correlated variants (D′=1, r2≥ 0.95), has previously been associated with risk for bipolar disorder. PMID:23089632

Perceived barriers for cannabis cessation: Relations to cannabis use problems, withdrawal symptoms, and self-efficacy for quitting.

PubMed

Zvolensky, Michael J; Paulus, Daniel J; Garey, Lorra; Manning, Kara; Hogan, Julianna B D; Buckner, Julia D; Rogers, Andrew H; Kathryn McHugh, R

2018-01-01

Cannabis is the most widely used illicit substance in the United States. Regular cannabis use appears to be a dynamic, chronic process consisting of multiple quit attempts, periods of reduction, periods of abstinence, and periods of continual use. Cannabis-related processes, including withdrawal, problematic consequences of use, and self-efficacy for quitting each contribute to the cycle of use and, in part, are maintained and reinforced by perceived barriers for cannabis cessation. Yet, no work has examined the association between perceived barriers for cannabis cessation and clinically-relevant processes related to cannabis use. To address this gap, the current study recruited a racially diverse sample (N=145, 63.4% Black or African American) of cannabis users from the community to test the hypothesis that greater perceived barriers for quitting cannabis was related to more cannabis use problems, more cannabis withdrawal symptoms, and lower self-efficacy for quitting cannabis. Structural equation modeling suggested that greater perceived barriers for quitting cannabis was uniquely associated with cannabis use problems (β=0.50, 95%CI [0.39, 0.65], p<0.001), greater withdrawal symptoms (β=0.39, 95%CI [0.30, 0.50], p<0.001), and lower self-efficacy for quitting (β=-0.17, 95%CI [-0.21, -0.02], p=0.028). The results of this study indicate perceived barriers for cannabis cessation may help in better understanding an array of clinically significant cannabis use processes. Indeed, the observed pattern of findings add to current theoretical models of substance use that aim to identify unique risk processes that may maintain substance use and provide valuable information that can be used to inform treatment for cannabis users. Published by Elsevier Ltd.

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...

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...

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.

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

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.

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

STEP signaling pathway mediates psychomotor stimulation and morphine withdrawal symptoms, but not for reward, analgesia and tolerance

PubMed Central

Kim, Yoon-Jung; Kang, Young; Park, Hye-Yeon; Lee, Jae-Ran; Yu, Dae-Yeul; Murata, Takuya; Gondo, Yoichi; Hwang, Jung Hwan; Kim, Yong-Hoon; Lee, Chul-Ho; Rhee, Myungchull; Han, Pyung-Lim; Chung, Bong-Hyun; Lee, Hyun-Jun; Kim, Kyoung-Shim

2016-01-01

Striatal-enriched protein tyrosine phosphatase (STEP) is abundantly expressed in the striatum, which strongly expresses dopamine and opioid receptors and mediates the effects of many drugs of abuse. However, little is known about the role of STEP in opioid receptor function. In the present study, we generated STEP-targeted mice carrying a nonsense mutation (C230X) in the kinase interaction domain of STEP by screening the N-ethyl-N-nitrosourea (ENU)-driven mutant mouse genomic DNA library and subsequent in vitro fertilization. It was confirmed that the C230X nonsense mutation completely abolished functional STEP protein expression in the brain. STEPC230X−/− mice showed attenuated acute morphine-induced psychomotor activity and withdrawal symptoms, whereas morphine-induced analgesia, tolerance and reward behaviors were unaffected. STEPC230X−/− mice displayed reduced hyperlocomotion in response to intrastriatal injection of the μ-opioid receptor agonist DAMGO, but the behavioral responses to δ- and κ-opioid receptor agonists remained intact. These results suggest that STEP has a key role in the regulation of psychomotor action and physical dependency to morphine. These data suggest that STEP inhibition may be a critical target for the treatment of withdrawal symptoms associated with morphine. PMID:26915673

Negative mood-induced alcohol-seeking is greater in young adults who report depression symptoms, drinking to cope, and subjective reactivity.

PubMed

Hogarth, Lee; Hardy, Lorna; Mathew, Amanda R; Hitsman, Brian

2018-04-01

Acute negative mood powerfully motivates alcohol-seeking behavior, but it remains unclear whether sensitivity to this effect is greater in drinkers who report depression symptoms, drinking to cope, and subjective reactivity. To examine these questions, 128 young adult alcohol drinkers (ages 18-25) completed questionnaires of alcohol use disorder symptoms, depression symptoms, and drinking to cope with negative affect. Baseline alcohol choice was measured by preference to enlarge alcohol versus food thumbnail images in two-alternative forced-choice trials. Negative mood was then induced by depressive statements and music, before alcohol choice was tested. Subjective reactivity was indexed by increased sadness pre- to post-mood induction. Baseline alcohol choice correlated with alcohol dependence symptoms (p = .001), and drinking coping motives (ps ≤ .01). Mood induction increased alcohol choice and subjective sadness overall (ps < .001). The mood-induced increase in alcohol choice was associated with depression symptoms (p = .007), drinking to cope (ps ≤ .03), and subjective reactivity (p = .007). The relationship between mood-induced alcohol choice and drinking to cope remained significant after covarying for other drinking motives. Furthermore, the three predictors (depression, drinking to cope, and subjective reactivity) accounted for unique variance in mood-induced alcohol choice (ps ≥ .03), and collectively accounted for 18% of the variance (p < .001). These findings validate the pictorial alcohol choice task as sensitive to the relative value of alcohol and acute negative mood. The findings also accord with the core prediction of negative reinforcement theory that sensitivity to the motivational impact of negative mood on alcohol-seeking behavior may be an important mechanism that links depression and alcohol dependence. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Negative Mood-Induced Alcohol-Seeking Is Greater in Young Adults Who Report Depression Symptoms, Drinking to Cope, and Subjective Reactivity

PubMed Central

2018-01-01

Acute negative mood powerfully motivates alcohol-seeking behavior, but it remains unclear whether sensitivity to this effect is greater in drinkers who report depression symptoms, drinking to cope, and subjective reactivity. To examine these questions, 128 young adult alcohol drinkers (ages 18–25) completed questionnaires of alcohol use disorder symptoms, depression symptoms, and drinking to cope with negative affect. Baseline alcohol choice was measured by preference to enlarge alcohol versus food thumbnail images in two-alternative forced-choice trials. Negative mood was then induced by depressive statements and music, before alcohol choice was tested. Subjective reactivity was indexed by increased sadness pre- to post-mood induction. Baseline alcohol choice correlated with alcohol dependence symptoms (p = .001), and drinking coping motives (ps ≤ .01). Mood induction increased alcohol choice and subjective sadness overall (ps < .001). The mood-induced increase in alcohol choice was associated with depression symptoms (p = .007), drinking to cope (ps ≤ .03), and subjective reactivity (p = .007). The relationship between mood-induced alcohol choice and drinking to cope remained significant after covarying for other drinking motives. Furthermore, the three predictors (depression, drinking to cope, and subjective reactivity) accounted for unique variance in mood-induced alcohol choice (ps ≥ .03), and collectively accounted for 18% of the variance (p < .001). These findings validate the pictorial alcohol choice task as sensitive to the relative value of alcohol and acute negative mood. The findings also accord with the core prediction of negative reinforcement theory that sensitivity to the motivational impact of negative mood on alcohol-seeking behavior may be an important mechanism that links depression and alcohol dependence. PMID:29389212

Risks for conduct disorder symptoms associated with parental alcoholism in stepfather families versus intact families from a community sample.

PubMed

Foley, Debra L; Pickles, Andrew; Rutter, Michael; Gardner, Charles O; Maes, Hermine H; Silberg, Judy L; Eaves, Lindon J

2004-05-01

It is not known if the prevalence of parental psychiatric disorders is higher in stepfather than intact families, or if parental alcoholism is differentially associated with risk for conduct disorder (CD) symptoms in stepfather families versus intact families. The sample comprised 839 girls and 741 boys from 792 intact families and 99 girls and 67 boys from 83 stepfather families from a population-based registry of twins aged between 8 and 17 years. Children's current psychiatric symptoms were assessed at personal interview with the child, mother and father. Parental histories of psychiatric disorder were assessed at personal interview with each residential parent. Associations between CD symptoms and parental alcoholism were characterized using both linear and Poisson regression, and results are presented with and without adjustment for maternal drug use during pregnancy, parental conflict, and estimated socioeconomic status (SES) based on census tract data. Mothers from stepfather families had a higher lifetime prevalence of alcoholism, antisocial personality disorder, depression and social phobia than mothers from intact families. Stepfathers had a higher lifetime prevalence of alcoholism and depression than biological fathers from intact families. Children from stepfather families had more externalizing (CD/ODD) symptoms than children from intact families. Girls who lived with an alcoholic stepfather had significantly more CD symptoms than girls who lived with an alcoholic biological father. Boys who lived with an alcoholic stepfather had significantly fewer CD symptoms than boys who lived with an alcoholic biological father. This sex difference was statistically significant. Adjustment for maternal drug use during pregnancy, parental conflict, and estimated SES based on census tract data did not change these findings. Children living in stepfather families are exposed to more parental psychiatric risk factors than children from intact families. The increased

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.

The association between alcohol use and depressive symptoms across socioeconomic status among 40- and 45-year-old Norwegian adults.

PubMed

Martinez, Priscilla; Neupane, Sudan Prasad; Perlestenbakken, Berit; Toutoungi, Christina; Bramness, Jørgen G

2015-11-19

Little population-based data among middle-aged adults exists examining the relationships between depressive symptoms, alcohol use, and socio-economic status (SES). This study aimed to describe the relationships between depressive symptoms and alcohol use at different levels of SES and to determine differences across SES levels among a population-based sample of 40 and 45 year old adults in Norway. This analysis was based on data from two Norwegian health studies conducted in 2000 and 2001, and included community-dwelling Norwegian men and women aged 40 and 45 years. Self-reported frequency and quantity of alcoholic drinks was used to calculate past-year typical quantity of drinks consumed and frequency of 5+ drinks per occasion, or heavy episodic drinking (HED). Depressive symptoms were assessed with the 10-item Hopkins Symptom Checklist, and SES was measured as education level and employment status. To observe the association between depressive symptoms and alcohol use at each level of SES we fitted multinomial logistic regression models using each alcohol outcome as a dependent variable stratified by level of education and employment. To observe differences across levels of SES, we examined the interaction between depressive symptoms and SES level in multinomial logistic regression models for each alcohol measures. Having depressive symptoms was significantly associated with an increased risk of 5+ typical drinks among people in the lowest (RRR = 1.60, p ≤ 0.05) education level, and not among people in the highest. Conversely, significant associations were observed among all levels of employment. For frequency of HED, depressive symptoms was not significantly associated with frequency of HED at any education level. Depressive symptoms was associated with 13+ past year HED episodes among people with no employment (RRR = 1.97, p ≤ 0.05), and part-time employment (RRR = 2.33, p ≤ 0.01), and no association was observed among people

The Effect of Co-occurring Substance Use on Gamma-hydroxybutyric Acid Withdrawal Syndrome.

PubMed

Kamal, Rama M; Dijkstra, Boukje A G; Loonen, Anton J; De Jong, Cornelis A J

2016-01-01

Gamma-hydroxybutyric acid (GHB) withdrawal is a complex syndrome which can be potentially life-threatening. Additionally, GHB-dependent patients frequently report co-occurring substance use of other psychoactive drugs. We assessed the add-on effect of co-use on GHB withdrawal symptoms. We conducted an open-label, pretest-posttest design study with 95 patients selected from 229 inpatients admitted for detoxification, who were divided into GHB only (GO, n = 40), GHB plus sedatives (GSE, n = 38), and GHB plus stimulants (GST, n = 17) groups. GHB withdrawal was evaluated by means of the Subjective Withdrawal Scale. Co-use add-on effects on the severity of withdrawal symptoms were evaluated 2.5 hours after the last illicit GHB self-administration (T1) when withdrawal was expected and 2.5 hours later, after administration of a very low dose of pharmaceutical GHB (T2). The GO group reported high scores of psychomotor retardation symptoms at both T1 and T2, and also high cravings, agitation, and restlessness at T1, and anxiety at T2. The GSE group reported the highest score in psycho-autonomic distress symptoms at both T1 and T2, whereas the GST group reported the highest score in psycho-motor stress factor at T2. There was no significant difference in withdrawal intensity in all symptom clusters between T1 and T2 for both GSE and GO groups. However, after 5 hours, the GST group reported significant decreases in intensity for all symptoms except for psycho-motor stress. At T1, GST and GSE groups reported more muscle twitches than the GO group as a significant add-on effect to the GHB withdrawal. At T2, the GST group experienced more agitation (P = 0.009), restlessness (P = 0.001), and rapid pulse (P = 0.034) than the GO group. Co-use, especially of stimulants, caused an add-on effect on the GHB withdrawal symptoms within the first 5 hours.

Alcohol and Nonmedical Prescription Drug Use to Cope With Posttraumatic Stress Disorder Symptoms: An Analysis of Hurricane Sandy Survivors.

PubMed

Lowe, Sarah R; Sampson, Laura; Young, Megan N; Galea, Sandro

2017-08-24

Postdisaster increases in substance use have been attributed to use of substances to cope with emotional reactions. However, no study to our knowledge has explored disaster survivors' substance use to cope with posttraumatic stress disorder (PTSD) symptoms. We investigated the prevalence and correlates of alcohol use and nonmedical prescription drug use (NMPDU) to cope with PTSD symptoms in two population-based samples of adult residents of New York City neighborhoods affected by Hurricane Sandy. Participants completed structured interviews at either 13-16 or 25-28 months postdisaster (combined N = 914). Participants with PTSD symptoms, assessed via the Posttraumatic Stress Checklist for DSM-5, indicated whether they coped with their symptoms through alcohol use or NMPDU, via items adapted from the National Epidemiologic Survey on Alcohol and Related Conditions. Logistic regression models explored correlates of substance use coping, including demographic characteristics, lifetime and hurricane-related exposures, and psychiatric symptoms in the combined sample. Over a third of participants in the combined sample (n = 311, 34.0%) reported PTSD symptoms, and of these, 12.8% used alcohol to cope and 9.2% endorsed NMPDU to cope. Older age and being a parent living with a child under 18 years old at the time of the hurricane were associated with a lower likelihood, and more severe depression symptoms with a higher likelihood, of alcohol use coping. Conclusions/Importance: Although preliminary, the results provide evidence for the use of substances to cope with postdisaster PTSD symptoms, and that age, parent status, and depression symptoms are associated with alcohol use coping.

Gender differences in trauma history and symptoms as predictors of relapse to alcohol and drug use.

PubMed

Heffner, Jaimee L; Blom, Thomas J; Anthenelli, Robert M

2011-01-01

The objective of this study was to determine whether there are gender-specific associations between trauma exposure and alcohol or drug relapse in alcohol-dependent adults. Participants were 51 men (n = 24) and women (n = 27) with alcohol dependence, 22 (43.1%) of whom relapsed during study participation. Severity of childhood trauma; number of lifetime events evoking fear, helplessness, or horror; and current trauma symptoms all predicted relapse in women, but not in men. These findings highlight the importance of assessing trauma history and providing treatment of trauma-related symptoms for individuals with alcohol and drug dependence, and for women in particular. © American Academy of Addiction Psychiatry.

Gender Differences in Trauma History and Symptoms as Predictors of Relapse to Alcohol and Drug Use

PubMed Central

Heffner, Jaimee L.; Blom, Thomas J.; Anthenelli, Robert M.

2011-01-01

The objective of this study was to determine whether there are gender-specific associations between trauma exposure and alcohol or drug relapse in alcohol dependent adults. Participants were 51 men (n=24) and women (n=27) with alcohol dependence, 22 (43.1%) of whom relapsed during study participation. Severity of childhood trauma; number of lifetime events evoking fear, helplessness, or horror; and current trauma symptoms all predicted relapse in women, but not in men. These findings highlight the importance of assessing trauma history and providing treatment of trauma-related symptoms for individuals with alcohol and drug dependence, and for women in particular. PMID:21679261

Prospective Assessment of Cannabis Withdrawal in Adolescents with Cannabis Dependence: A Pilot Study

ERIC Educational Resources Information Center

Milin, Robert; Manion, Ian; Dare, Glenda; Walker, Selena

2008-01-01

A study to identify and assess the withdrawal symptoms in adolescents afflicted with cannabis dependence is conducted. Results conclude that withdrawal symptoms of cannabis were present in adolescents seeking treatment for this substance abuse.

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

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.

Predictors of nicotine withdrawal symptoms: findings from the first randomized smoking cessation trial in a low-income country setting.

PubMed

Ben Taleb, Ziyad; Ward, Kenneth D; Asfar, Taghrid; Jaber, Rana; Auf, Rehab; Maziak, Wasim

2016-07-01

To identify predictors of nicotine withdrawal symptoms among smokers who participated in a randomized cessation trial in a low-income country. We analyzed data from 269 smokers who participated in a randomized, placebo-controlled smoking cessation trial conducted in primary healthcare in Aleppo, Syria. All participants received behavioral counseling and were randomized to receive either 6 weeks of nicotine or placebo patch and were followed for one year. Throughout the study, lower total withdrawal score was associated with greater education (p = 0.044), older age of smoking initiation (p = 0.017), lower nicotine dependence (p = 0.024), higher confidence in ability to quit (p = 0.020), lower reported depression (p < 0.001), higher adherence to patch (p = 0.026), belief of receiving nicotine patches rather than placebo (p = 0.011), and waterpipe use (p = 0.047). Lower nicotine dependence, greater educational attainment, higher confidence in ability to quit and waterpipe use predict lower withdrawal severity. Waterpipe smoking may serve as a barrier to smoking cessation efforts in countries where its use is highly prevalent. Further, expectancies about the effects of pharmacotherapy appear to mediate the experience of nicotine withdrawal.

Course of alcohol symptoms and social anxiety disorder from adolescence to young adulthood.

PubMed

Black, Jessica J; Clark, Duncan B; Martin, Christopher S; Kim, Kevin H; Blaze, Thomas J; Creswell, Kasey G; Chung, Tammy

2015-06-01

There is limited knowledge of the course of social anxiety disorder (SAD) from adolescence into adulthood, and how SAD and alcohol use disorder (AUD) symptoms change together over time. The current study examined how persistent and adolescent-limited SAD relate to alcohol symptom trajectories across adolescence and into adulthood, as well as gender differences in the course of SAD and AUD symptoms. Participants were 788 youth (ages 12 to 18 at the baseline assessment; 46.2% female; 80.5% White) recruited from the community (n = 220) and from clinical programs (n = 568). Youth completed clinical interviews on their lifetime history of AUD symptoms and SAD at baseline and were followed through age 25. Multivariate polynomial growth mixture modeling was used to estimate developmental trajectories for SAD and AUD symptoms separately, then together in a dual trajectory model. Gender differences were examined using a classify-analyze approach. Three SAD trajectory classes were identified: adolescent-limited (15%), persistent (6%), and no SAD (79%). For AUD symptoms, 5 trajectories were identified: severe (10%), moderate (22%), remitting (18%), young adult onset (22%), and stable low (28%). Those with a history of SAD were about twice as likely to be in the severe AUD symptom class compared to those without a history of SAD. Compared to those with persisting SAD, those in the adolescent-limited SAD class were more likely to belong to the stable low AUD trajectory. Compared to males with SAD, females with SAD were less likely to be in the moderate AUD symptom class and were more likely to be in stable low and young adult onset AUD symptom classes. A history of SAD was associated with membership in the severe AUD trajectory group. The association of gender with SAD and AUD differed depending on developmental period. Future research should examine whether treating SAD in early adolescence may prevent subsequent AUD symptoms. Copyright © 2015 by the Research Society on

The Dimensionality of DSM-IV Alcohol Use Disorders among Adolescent and Adult Drinkers and Symptom Patterns by Age, Gender, and Race/Ethnicity

PubMed Central

Harford, Thomas C.; Yi, Hsiao-ye; Faden, Vivian B.; Chen, Chiung M.

2015-01-01

Background There is limited information on the validity of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) alcohol use disorders (AUD) symptom criteria among adolescents in the general population. The purpose of the present study is to assess the DSM-IV AUD symptom criteria as reported by adolescent and adult drinkers in a single representative sample of the U.S. population ages 12 years and older. This design avoids potential confounding due to differences in survey methodology when comparing adolescents and adults from different surveys. Methods A total of 133,231 current drinkers (had at least one drink in the past year) ages 12 years and older were drawn from respondents to the 2002–2005 National Surveys on Drug Use and Health. DSM-IV AUD criteria were assessed by questions related to specific symptoms occurring during the past 12 months. Factor analytic (FA) and item response theory (IRT) models were applied to the 11 AUD symptom criteria to assess the probabilities of symptom item endorsements across different values of the underlying trait. Results A one-factor model provided an adequate and parsimonious interpretation for the 11 AUD criteria for the total sample and for each of the gender-age groups. The MIMIC model exhibited significant indication for item bias among some criteria by gender, age, and race/ethnicity. Symptom criteria for “tolerance,” “time spent,” and “hazardous use” had lower item thresholds (i.e., lower severity) and low item discrimination, and they were well separated from the other symptoms, especially in the two younger age groups (12–17 and 18–25). “Larger amounts,” “cut down,” “withdrawal,” and “legal problems” had higher item thresholds but generally lower item discrimination, and they tend to exhibit greater dispersion at higher AUD severity, particularly in the youngest age group (12–17). Conclusions Findings from the present study do not provide support for the

The dimensionality of DSM-IV alcohol use disorders among adolescent and adult drinkers and symptom patterns by age, gender, and race/ethnicity.

PubMed

Harford, Thomas C; Yi, Hsiao-ye; Faden, Vivian B; Chen, Chiung M

2009-05-01

There is limited information on the validity of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) alcohol use disorders (AUD) symptom criteria among adolescents in the general population. The purpose of this study is to assess the DSM-IV AUD symptom criteria as reported by adolescent and adult drinkers in a single representative sample of the U.S. population aged 12 years and older. This design avoids potential confounding due to differences in survey methodology when comparing adolescents and adults from different surveys. A total of 133,231 current drinkers (had at least 1 drink in the past year) aged 12 years and older were drawn from respondents to the 2002 to 2005 National Surveys on Drug Use and Health. DSM-IV AUD criteria were assessed by questions related to specific symptoms occurring during the past 12 months. Factor analytic and item response theory models were applied to the 11 AUD symptom criteria to assess the probabilities of symptom item endorsements across different values of the underlying trait. A 1-factor model provided an adequate and parsimonious interpretation for the 11 AUD criteria for the total sample and for each of the gender-age groups. The MIMIC model exhibited significant indication for item bias among some criteria by gender, age, and race/ethnicity. Symptom criteria for "tolerance,"time spent," and "hazardous use" had lower item thresholds (i.e., lower severity) and low item discrimination, and they were well separated from the other symptoms, especially in the 2 younger age groups (12 to 17 and 18 to 25). "Larger amounts,"cut down,"withdrawal," and "legal problems" had higher item thresholds but generally lower item discrimination, and they tend to exhibit greater dispersion at higher AUD severity, particularly in the youngest age group (12 to 17). Findings from the present study do not provide support for the 2 separate DSM-IV diagnoses of alcohol abuse and dependence among either adolescents or adults

Nicotine levels, withdrawal symptoms, and smoking reduction success in real world use: A comparison of cigarette smokers and dual users of both cigarettes and E-cigarettes.

PubMed

Jorenby, Douglas E; Smith, Stevens S; Fiore, Michael C; Baker, Timothy B

2017-01-01

To evaluate how experienced dual users used cigarettes and e-cigarettes in real-world use and under different levels of cigarette availability. Dual users (cigarettes+e-cigarettes; n=74) and a smoke-only group (just cigarettes; n=74) engaged in a 26-day study with two ad lib use intervals, a week of 75% cigarette reduction and three days of 100% cigarette reduction. After a week of ad lib use of products, all participants were asked to reduce smoking by 75% (dual users were free to use their e-cigarettes as they wished), followed by another week of ad lib use. All participants were then asked to reduce smoking by 100% (cessation) for three days. Primary outcomes were biological samples (carbon monoxide, urinary nicotine and cotinine). Participants also provided real-time reports of product use, craving, and withdrawal symptoms using a smartphone app. Dual users did not smoke fewer cigarettes than smoke-only participants during ad lib periods, but quadrupled their use of e-cigarettes during smoking reduction periods. Dual users were significantly more likely to maintain 100% reduction (97.1% vs. 81.2%). Amongst women, dual use was associated with higher nicotine levels and withdrawal suppression. Among a group of experienced dual users, e-cigarettes helped maintain smoking reduction and reduced some withdrawal symptoms, although both withdrawal symptoms and nicotine levels varied as a function of gender. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Nicotine Levels, Withdrawal Symptoms, and Smoking Reduction Success in Real World Use: A Comparison of Cigarette Smokers and Dual Users of Both Cigarettes and E-Cigarettes

PubMed Central

Jorenby, Douglas E.; Smith, Stevens S.; Fiore, Michael C.; Baker, Timothy B.

2016-01-01

Introduction To evaluate how experienced dual users used cigarettes and e-cigarettes in real-world use and under different levels of cigarette availability. Methods Dual users (cigarettes + e-cigarettes; n=74) and a smoke-only group (just cigarettes; n=74) engaged in a 26-day study with two ad lib use intervals, a week of 75% cigarette reduction and three days of 100% cigarette reduction. After a week of ad lib use of products, all participants were asked to reduce smoking by 75% (dual users were free to use their e-cigarettes as they wished), followed by another week of ad lib use. All participants were then asked to reduce smoking by 100% (cessation) for three days. Primary outcomes were biological samples (carbon monoxide, urinary nicotine and cotinine). Participants also provided real-time reports of product use, craving, and withdrawal symptoms using a smartphone app. Results Dual users did not smoke fewer cigarettes than smoke-only participants during ad lib periods, but quadrupled their use of e-cigarettes during smoking reduction periods. Dual users were significantly more likely to maintain 100% reduction (97.1% vs. 81.2%). Amongst women, dual use was associated with higher nicotine levels and withdrawal suppression. Discussion Among a group of experienced dual users, e-cigarettes helped maintain smoking reduction and reduced some withdrawal symptoms, although both withdrawal symptoms and nicotine levels varied as a function of gender. PMID:27883949

Patterns of change in withdrawal symptoms, desire to smoke, reward motivation, and response inhibition across three months of smoking abstinence

PubMed Central

Dawkins, Lynne; Powell, Jane H.; Pickering, Alan; Powell, John; West, Robert

2009-01-01

Aims We have previously demonstrated that acute smoking abstinence is associated with lowered reward motivation and impaired response inhibition. This prospective study explores whether these impairments, along with withdrawal-related symptoms, recover over three months of sustained abstinence. Design Participants completed a 12-hour abstinent baseline assessment and were then randomly allocated to quit unaided or continue smoking. All were re-tested after 7 days, 1 month and 3 months. Successful quitters’ scores were compared with those of continuing smokers, who were tested after ad libitum smoking. Setting Goldsmiths, University of London. Participants 33 smokers who maintained abstinence to 3 months, and 31 continuing smokers. Measurements Indices previously demonstrated in this cohort of smokers to be sensitive to the effect of nicotine vs. acute abstinence: reward motivation (SHAPS, CARROT, Stroop); tasks of response inhibition (antisaccade task; CPT) and clinical indices of mood (HADS), withdrawal symptoms (MPSS) and desire to smoke. Findings SHAPS anhedonia and reward responsivity (CARROT) showed significant improvement and plateaued after a month of abstinence, not differing from the scores of continuing smokers tested in a satiated state. Mood, other withdrawal symptoms and desire to smoke all declined from acute abstinence to 1 month of cessation and were equivalent, or lower than, the levels reported by continuing, satiated smokers. Neither group showed a change in CPT errors over time whilst continuing smokers, but not abstainers, showed improved accuracy on the antisaccade task at 3 months. Conclusion Appetitive processes and related affective states appear to improve in smokers who remain nicotine-free for 3 months whereas response inhibition does not. Although in need of replication, the results tentatively suggest that poor inhibitory control may constitute a long-term risk factor for relapse and could be a target for intervention. PMID:19344444

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

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

Evaluating Age Differences in Coping Motives as a Mediator of the Link between Social Anxiety Symptoms and Alcohol Problems

PubMed Central

Clerkin, Elise M.; Werntz, Alexandra J.; Magee, Joshua C.; Lindgren, Kristen P.; Teachman, Bethany A.

2014-01-01

The goal of this study is to evaluate whether coping motives mediate the relationship between self-reported symptoms of social anxiety and alcohol problems across different age groups, building upon previous research conducted among emerging adults. This study focuses on adult drinkers, including emerging adults (age 18–25; n = 148), young adults (age 26–39; n = 68), and middle-aged adults (age 40–65; n = 51). All participants completed measures of social anxiety symptoms, alcohol problems, and coping motives, administered via the web. Invariance tests using structural equation modeling suggested that among emerging adults (and to some degree middle-aged adults), coping motives mediated the positive relationship between symptoms of social anxiety and alcohol problems. Interestingly, coping motives appeared to suppress a negative relationship between social anxiety and alcohol problems in young adults. Results suggest that it is critical to consider age differences when attempting to understand the relationships between symptoms of social anxiety, alcohol problems, and coping motives. PMID:24841182

Evaluating age differences in coping motives as a mediator of the link between social anxiety symptoms and alcohol problems.

PubMed

Clerkin, Elise M; Werntz, Alexandra J; Magee, Joshua C; Lindgren, Kristen P; Teachman, Bethany A

2014-09-01

The goal of this study is to evaluate whether coping motives mediate the relationship between self-reported symptoms of social anxiety and alcohol problems across different age groups, building on previous research conducted among emerging adults. This study focuses on adult drinkers, including emerging adults (aged 18-25 years; n = 148), young adults (aged 26-39 years; n = 68), and middle-aged adults (aged 40-65 years; n = 51). All participants completed measures of social anxiety symptoms, alcohol problems, and coping motives, administered via the Web. Invariance tests using structural equation modeling suggested that among emerging adults (and to some degree middle-aged adults), coping motives mediated the positive relationship between symptoms of social anxiety and alcohol problems. Interestingly, coping motives appeared to suppress a negative relationship between social anxiety and alcohol problems in young adults. Results suggest that it is critical to consider age differences when attempting to understand the relationships between symptoms of social anxiety, alcohol problems, and coping motives.

Alcohol use disorders in Iran: Prevalence, symptoms, correlates, and comorbidity.

PubMed

Amin-Esmaeili, Masoumeh; Rahimi-Movaghar, Afarin; Sharifi, Vandad; Hajebi, Ahmad; Mojtabai, Ramin; Radgoodarzi, Reza; Hefazi, Mitra; Motevalian, Abbas

2017-07-01

For nearly four decades, alcohol production and consumption has been banned in the Islamic country of Iran. However, little is known about the extent of alcohol use and associated problems in the country. The paper aims to present findings on the 12-month prevalence, symptoms, severity, correlates, and comorbidity of alcohol use disorders in the Iranian population. This report is based on the 2011 Iranian household Mental Health survey (IranMHS), a nationally representative face-to-face household survey with a multi-stage, cluster sampling design. A total of 7840 individuals aged 15-64 responded to the alcohol section. We assessed 12-month alcohol use disorders according to DSM-IV and DSM-5 criteria and harmful use according to the ICD-10 criteria. Weighted prevalence of using alcohol at least once in the past 12 months was 5.7%. The prevalence of 12-month alcohol use disorders was 1% according to DSM-IV criteria and 1.3% according to DSM-5. Harmful use was reported in 0.6%. Alcohol use disorders were markedly more common in men than women with an odds ratio (OR) of 13.3. It was also more prevalent in never-married versus married individuals (OR=2.5) and in those living in urban versus rural areas (OR=2.4). Among those with alcohol use disorders, 46.3% had a concurrent mood or anxiety disorder. Aggressive behaviors and injuries were more likely in those with alcohol use disorders. Although Iran has a low level of alcohol use, its adverse consequences including use disorders, aggression, and injuries are moderately common and raise serious public health concerns. Copyright © 2017 Elsevier B.V. All rights reserved.

Racial/ethnic discrimination, posttraumatic stress symptoms, and alcohol problems in a longitudinal study of Hispanic/Latino college students.

PubMed

Cheng, Hsiu-Lan; Mallinckrodt, Brent

2015-01-01

Racial/ethnic discrimination has been identified as a risk factor in the development of posttraumatic stress disorder (PTSD) symptoms in persons of color (Carter, 2007). Many persons, regardless of race/ethnicity, with PTSD symptoms resulting from combat, violent crimes, sexual assault, or natural disasters use alcohol in an attempt to cope. This longitudinal study surveyed 203 Hispanic/Latino students twice at approximately a 1-year interval, and used a cross-lagged design to compare Time 1 links from alcohol use and experiences of discrimination with the same variables at Time 2, plus symptoms of PTSD. Each survey included the General Ethnic Discrimination scale and the Alcohol Use Disorders Identification Test. Only Time 2 packets contained the Posttraumatic Stress Disorder Checklist-Civilian. Cross-lagged analyses conducted by comparing nested structural equation models found that fixing the causal paths to zero from Time 1 experiences of discrimination to Time 2 alcohol problems and PTSD resulted in a significantly worse fit of the data. However, fixing the paths to zero from Time 1 maladaptive alcohol use to Time 2 PTSD and experiences of discrimination resulted in no significant difference in model fit. Thus, this pattern of findings is consistent with an inference that Hispanic/Latino college students who experience racial/ethnic discrimination are at risk for developing symptoms of posttraumatic stress and increased maladaptive alcohol use; conversely, maladaptive alcohol use does not appear to be a risk factor for later experiences of discrimination or PTSD symptoms. PsycINFO Database Record (c) 2015 APA, all rights reserved.

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

The pathogenesis of propranolol-withdrawal syndrome in essential hypertension.

PubMed

Kristensen, B O; Steiness, E; Weeke, J

1979-12-01

1. In hypertension, the beta-adrenoreceptor-blocker-withdrawal syndrome comprises tachycardia, sweating, tremor and general malaise, symptoms resembling thyrotoxicosis. 2. The effect of abrupt cessation of propranolol on serum concentrations of thyroxine (T4) and triiodothyronine (T3) was therefore investigated in five patients with uncomplicated essential hypertension, treated with propranolol in doses from 160 to 480 mg/day. 3. Four of the five patients developed one or more of the above-mentioned symptoms within 2-6 days after withdrawal of propranolol. 4. A mean relative increase in serum free T3 of 51% (range 22-74%) was found in these four patients on the day of onset of symptoms. 5. The increase in free T3 in the five patients correlated positively with total serum propranolol on the last day the drug was given (r = 0.91, 2P = 0.03). 6. As an increase in T3 was found only in patients suffering the withdrawal syndrome, and was maximal the day the symptoms appeared, despite a variation in time of onset from 2 to 6 days, it is suggested that the beta-adrenoreceptor-blocker-withdrawal syndrome, at least partially, is caused by rebound increased production of T3, induced by the well-known inhibition of the monodeiodination of T4 to T3 during beta-adrenoreceptor blockade. 7. This assumption may explain the clinical symptoms and the reported transient increased beta-adrenoreceptor sensitivity with unchanged serum concentrations of catecholamines.

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

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.

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.

Depressive symptoms and hazardous/harmful alcohol use are prevalent and correlate with stigma among TB-HIV patients in Lesotho.

PubMed

Hayes-Larson, E; Hirsch-Moverman, Y; Saito, S; Frederix, K; Pitt, B; Maama-Maime, L; Howard, A A

2017-11-01

Limited data exist on the prevalence and correlates, including stigma, of mental health conditions, including depressive symptoms and alcohol use, among patients co-infected with tuberculosis (TB) and the human immunodeficiency virus (HIV) in sub-Saharan Africa, despite their negative impact on health outcomes. To assess the prevalence and correlates of depressive symptoms and hazardous/harmful alcohol use among TB-HIV patients in the Start TB patients on ART and Retain on Treatment (START) study. START, a mixed-methods cluster-randomized trial, evaluated a combination intervention package vs. standard of care (SOC) to improve treatment outcomes in TB-HIV co-infected patients in Lesotho. Moderate/severe depressive symptoms and hazardous/harmful alcohol use were measured using baseline questionnaire data collected from April 2013 to March 2015. Demographic, psychosocial, and TB- and HIV-related knowledge and attitudes, including stigma, were assessed for association with both conditions using generalized linear mixed models. Among 371 participants, 29.8% reported moderate/severe depressive symptoms, and 24.7% reported hazardous/harmful alcohol use; 7% reported both. Depressive symptoms were significantly associated with less education, more difficulty understanding written medical information, non-disclosure of TB, greater TB stigma, and the SOC study arm. Hazardous/harmful alcohol use was significantly associated with male sex, as well as greater TB and external HIV stigma. Prevalence of depressive symptoms and hazardous/harmful alcohol use were high, suggesting a need for routine screening for, and treatment of, mental health disorders in TB-HIV patients.

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

Nabilone therapy for cannabis withdrawal presenting as protracted nausea and vomiting.

PubMed

Lam, Philip W; Frost, David W

2014-09-22

Cannabis is one of the most commonly used recreational drugs worldwide. Psychoactive properties of the principal compound, δ-9-tetrahydrocannabinol include euphoria, a sense of relaxation and increased appetite. Chronic cannabis use has been associated with the development of a withdrawal syndrome on abrupt discontinuation. Withdrawal symptoms typically begin within 24 h of abstinence and manifest as irritability, nervousness, sleep disturbances and decreased appetite. There is growing evidence that supports the use of plant-derived and synthetic cannabinoids for the treatment of cannabis withdrawal. In this case report, we present 20-year-old woman who developed protracted nausea and vomiting secondary to cannabis withdrawal and was successfully treated with nabilone. Nausea and vomiting is not listed in the Diagnostic and Statistical Manual-5 diagnostic criteria for cannabis withdrawal syndrome and is an uncommon symptom presentation. 2014 BMJ Publishing Group Ltd.

Alcohol Consumption and Factors Associated with Depressive Symptoms among Older Adults in Mainland China

ERIC Educational Resources Information Center

Liu, Yujun; Xie, Yimeng; Brossoie, Nancy; Roberto, Karen A.; Redican, Kerry J.

2017-01-01

Background: High levels of alcohol consumption have been shown to be related to cardiovascular disease, cancer, diabetes, and other chronic disease and is an important variable in the global burden of disease. Purpose: This study explored the relationship between alcohol consumption and depressive symptoms among older Chinese adults in mainland…

Adult attention deficit hyperactivity disorder symptom profiles and concurrent problems with alcohol and cannabis: sex differences in a representative, population survey.

PubMed

Kolla, Nathan J; van der Maas, Mark; Toplak, Maggie E; Erickson, Patricia G; Mann, Robert E; Seeley, Jane; Vingilis, Evelyn

2016-02-27

Adult attention deficit hyperactivity disorder (ADHD) shows a robust association with alcohol and cannabis misuse, and these relationships are expressed differently in males and females. Manifestation of specific ADHD symptom profiles, even in the absence of the full disorder, may also be related to problems with alcohol and cannabis, although these relationships have not been investigated in epidemiological studies. To address this question, we studied the sex-specific associations of ADHD symptomatology with problematic alcohol and cannabis use in a representative sample of adults aged 18 years and older residing in Ontario, Canada. Data were obtained from the Centre for Addiction and Mental Health Monitor, an ongoing cross-sectional telephone survey, between January 2011 and December 2013. Respondents (n =  5080) reported on current ADHD symptomatology, measured using the Adult ADHD Self-Report Version 1.1 Screener (ASRS-V1.1) and four additional items, and alcohol and cannabis use, which were measured using the Alcohol Use Disorders Identification Test (AUDIT) and the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), respectively. Logistic regression analyses were conducted in men and women to test the association of each ADHD symptom cluster (hyperactivity, inattentiveness, impulsivity) with problematic alcohol and cannabis use. After controlling for age, education, and comorbid internalizing and externalizing psychopathology, hyperactive symptoms were associated with problematic alcohol use in both men and women and with problematic cannabis use in men. Impulsive symptoms were independently associated with problematic cannabis use in men. By contrast, inattentive symptomatology predicted problems with alcohol and cannabis only in women. In all models, age was negatively associated with substance misuse and externalizing behavior was positively correlated and the strongest predictor of hazardous alcohol and cannabis use. ADHD symptom

Evidence of the Impact of Diet, Fluid Intake, Caffeine, Alcohol and Tobacco on Lower Urinary Tract Symptoms: A Systematic Review.

PubMed

Bradley, Catherine S; Erickson, Bradley A; Messersmith, Emily E; Pelletier-Cameron, Anne; Lai, H Henry; Kreder, Karl J; Yang, Claire C; Merion, Robert M; Bavendam, Tamara G; Kirkali, Ziya

2017-11-01

Diet, fluid intake and caffeine, alcohol and tobacco use may have effects on lower urinary tract symptoms. Constructive changes in these modifiable nonurological factors are suggested to improve lower urinary tract symptoms. To better understand the relationship between nonurological factors and lower urinary tract symptoms, we performed a systematic literature review to examine, grade and summarize reported associations between lower urinary tract symptoms and diet, fluid intake and caffeine, tobacco and alcohol use. We performed PubMed® searches for eligible articles providing evidence on associations between 1 or more nonurological factors and lower urinary tract symptoms. A modified Oxford scale was used to grade the evidence. We reviewed 111 articles addressing diet (28 studies), fluid intake (21) and caffeine (21), alcohol (26) and tobacco use (44). The evidence grade was generally low (6% level 1, 24% level 2, 11% level 3 and 59% level 4). Fluid intake and caffeine use were associated with urinary frequency and urgency in men and women. Modest alcohol use was associated with decreased likelihood of benign prostatic hyperplasia diagnosis and reduced lower urinary tract symptoms in men. Associations between lower urinary tract symptoms and ingestion of certain foods and tobacco were inconsistent. Evidence of associations between lower urinary tract symptoms and diet, fluid intake and caffeine, alcohol and tobacco use is sparse and mostly observational. However, there is evidence of associations between increased fluid and caffeine intake and urinary frequency/urgency, and between modest alcohol intake and decreased benign prostatic hyperplasia diagnosis and lower urinary tract symptoms. Given the importance of these nonurological factors in daily life, and their perceived impact on lower urinary tract symptoms, higher quality evidence is needed. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All

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.

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

[Treatment of gamma-hydroxybutyrate withdrawal].

PubMed

Strand, Niels August Willer; Petersen, Tonny Studsgaard; Nielsen, Lars Martin; Boegevig, Soren

2017-12-11

Gamma-hydroxybutyrate (GHB) is a drug of abuse, for which physical addiction develops quickly. GHB withdrawal can develop into a life-threatening condition and has previously been treated mainly with benzodiazepines. These have not always proven effective, leading to long hospitalizations in intensive care units. Based on successful Dutch treatment results for using GHB to treat GHB withdrawal symptoms, we propose to implement a similar method in Denmark. The method requires an interdisciplinary effort for which The Danish Poison Information Centre should be consulted for expertise.

Depressive Symptoms Anticipate Changes in the Frequency of Alcohol Intoxication Among Low-Accepted Adolescents

PubMed Central

Richmond, Ashley D.; Laursen, Brett; Kerr, Margaret; Stattin, Håkan

2015-01-01

Objective: There is strong evidence that depression anticipates later drinking problems among adults. These associations have not been consistently documented during adolescence, perhaps because little attention has been given to individual differences in peer relationships, which are the primary setting for adolescent alcohol consumption. This study investigated associations between depressive affect and alcohol misuse as moderated by peer group acceptance. Method: A community sample of 1,048 Swedish youth provided self-reports of depressive symptoms and intoxication frequency at annual intervals across the middle school years (seventh grade: M = 13.21 years old; eighth grade: M = 14.27 years old; ninth grade: M = 15.26 years old). Peer nominations provided a measure of individual acceptance. Results: Growth curve analyses revealed differences in the extent to which initial levels of depressive symptoms predicted the slope of increase in intoxication frequency. Higher levels of depressive symptoms at the outset anticipated sharp increases in intoxication frequency from seventh to ninth grades for low-accepted youth but not for average- or high-accepted youth. Conclusions: poor peer relations and depressive affect are vulnerabilities that set the stage for escalating adolescent alcohol misuse. Across the middle school years, when most youth have their first experiences with alcohol, peer difficulties exacerbated the tendency of depressed youth to drink to excess. PMID:26098034

The combination very low-dose naltrexone-clonidine in the management of opioid withdrawal.

PubMed

Mannelli, Paolo; Peindl, Kathleen; Wu, Li-Tzy; Patkar, Ashwin A; Gorelick, David A

2012-05-01

The management of withdrawal absorbs substantial clinical efforts in opioid dependence (OD). The real challenge lies in improving current pharmacotherapies. Although widely used, clonidine causes problematic adverse effects and does not alleviate important symptoms of opioid withdrawal, alone or in combination with the opioid antagonist naltrexone. Very low-dose naltrexone (VLNTX) has been shown to attenuate withdrawal intensity and noradrenaline release following opioid agonist taper, suggesting a combination with clonidine may result in improved safety and efficacy. We investigated the effects of a VLNTX-clonidine combination in a secondary analysis of data from a double-blind, randomized opioid detoxification trial. Withdrawal symptoms and treatment completion were compared following VLNTX (.125 or .25 mg/day) and clonidine (.1-.2 mg q6h) in 127 individuals with OD undergoing 6-day methadone inpatient taper at a community program. VLNTX was more effective than placebo or clonidine in reducing symptoms and signs of withdrawal. The use of VLNTX in combination with clonidine was associated with attenuated subjective withdrawal compared with each medication alone, favoring detoxification completion in comparison with clonidine or naltrexone placebo. VLNTX/clonidine was effective in reducing symptoms that are both undertreated and well controlled with clonidine treatment and was not associated with significant adverse events compared with other treatments. Preliminary results elucidate neurobiological mechanisms of OD and support the utility of controlled studies on a novel VLNTX + low-dose clonidine combination for the management of opioid withdrawal.

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

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.

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

Examination of the dynamic interplay between posttraumatic stress symptoms and alcohol misuse among combat-exposed Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) Veterans.

PubMed

Langdon, Kirsten J; Fox, Annie B; King, Lynda A; King, Daniel W; Eisen, Susan; Vogt, Dawne

2016-05-15

Although alcohol misuse co-occurs with PTSD symptoms at a strikingly high rate (i.e., nearly 52% of men and 28% of women with PTSD also meet diagnostic criteria for an Alcohol Use Disorder), the functional associations between these symptom types remain unclear. The current study sought to clarify the nature of posttraumatic stress-alcohol misuse relations by employing a prospective longitudinal methodology-the latent difference score approach-to examine dynamic change in posttraumatic stress symptoms and alcohol misuse among 478 combat-exposed Veterans completing a longitudinal survey of post-deployment mental and physical health. This study builds on the existing literature, as most prior research has been limited to cross-sectional studies and has not explored prospective relations between specific PTSD symptom clusters and alcohol misuse. Consistent with the self-medication model, results indicated that PTSD symptoms demonstrate a prospective and proximal association with alcohol misuse during the assessment period; however, alcohol misuse did not appear to be a unique contributor to overall PTSD symptom exacerbation over time. Examination of individual PTSD symptom clusters revealed that more severe symptoms of intrusion and numbing, but not avoidance and hyperarousal, predicted greater alcohol misuse at subsequent time intervals. The constructs examined within this investigation relied on self-report data; diagnostic criteria for PTSD and/or Alcohol Use Disorders were not assessed. Future work may benefit from replicating these findings in clinical populations formally diagnosed with PTSD via clinician-administered structured interviews. Findings underscore the importance of addressing PTSD symptoms in the context of alcohol treatment to facilitate improved drinking outcomes. Copyright © 2016 Elsevier B.V. All rights reserved.

Examination of the Dynamic Interplay between Posttraumatic Stress Symptoms and Alcohol Misuse among Combat-Exposed Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) Veterans

PubMed Central

Langdon, Kirsten J.; Fox, Annie B.; King, Lynda A.; King, Daniel W.; Eisen, Susan; Vogt, Dawne

2016-01-01

Background Although alcohol misuse co-occurs with PTSD symptoms at a strikingly high rate (i.e., nearly 52% of men and 28% of women with PTSD also meet diagnostic criteria for an Alcohol Use Disorder; Kessler et al., 1995), the functional associations between these symptom types remain unclear. Methods The current study sought to clarify the nature of posttraumatic stress-alcohol misuse relations by employing a prospective longitudinal methodology - the latent difference score approach - to examine dynamic change in posttraumatic stress symptoms and alcohol misuse among 478 combat-exposed Veterans completing a longitudinal survey of post-deployment mental and physical health. This study builds on the existing literature, as most prior research has been limited to cross-sectional studies and has not explored prospective relations between specific PTSD symptom clusters and alcohol misuse. Results Consistent with the self-medication model, results indicated that PTSD symptoms demonstrate a prospective and proximal association with alcohol misuse during the assessment period; however, alcohol misuse did not appear to be a unique contributor to overall PTSD symptom exacerbation over time. Examination of individual PTSD symptom clusters revealed that more severe symptoms of intrusion and numbing, but not avoidance and hyperarousal, predicted greater alcohol misuse at subsequent time intervals. Limitations The constructs examined within this investigation relied on self-report data; diagnostic criteria for PTSD and/or Alcohol Use Disorders were not assessed. Future work may benefit from replicating these findings in clinical populations formally diagnosed with PTSD via clinician-administered structured interviews. Conclusions Findings underscore the importance of addressing PTSD symptoms in the context of alcohol treatment to facilitate improved drinking outcomes. PMID:26938966