sodium oxybate [mesh] and alcohol-related disorders [mesh]

45 articles - 08.02.10

1: Expert Opin Investig Drugs. 2009 May;18(5):675-86.

The therapeutic potential of gamma-hydroxybutyric acid for alcohol dependence: balancing the risks and benefits. A focus on clinical data.

Addolorato G, Leggio L, Ferrulli A, Caputo F, Gasbarrini A.

Catholic University of Rome, Institute of Internal Medicine, L.o A. Gemelli 8, I-00168 Rome, Italy. g.addolorato@rm.unicatt.it

There is an increasing interest in studying the role of GABAergic medications in the treatment of alcohol dependence. The GABAergic drug gamma-hydroxybutyric acid (GHB) has been investigated in Europe as a possible treatment for alcohol dependence. In some European Countries, GHB has been approved as a treatment for alcohol dependence. However, this drug has also shown addictive properties, therefore raising questions about its safety in treating alcohol-dependent subjects. More recent research is focusing on the possibility of identifying alcohol-dependent subtypes without risk of developing GHB abuse. Finally, GHB and naltrexone combined together represent a possible approach deserving future investigations.

Publication Types: Review

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19379123&dopt=ExternalLink

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2: J Forensic Leg Med. 2009 Apr;16(3):148-51. Epub 2008 Oct 29.

What constitutes a normal ante-mortem urine GHB concentration?

Mari F, Politi L, Trignano C, Di Milia MG, Di Padua M, Bertol E.

Forensic Toxicology Division, Department of Anatomy, Histology and Legal Medicine, University of Florence, Italy. francesco.mari@unifi.it

Gamma-hydroxybutyric acid (GHB) is endogenously produced within the central nervous system, however it is also used as a medication for the treatment of a variety of clinical conditions, sold under the name Zyrem in the United States and Alcover in Europe. It is a very dangerous drug with a very limited safety margin, and is classified as a controlled substance in many countries. The interpretation of post-mortem studies of GHB concentrations is problematic; GHB can be detected in urine and blood from non-GHB users, both before and after death, and concentrations in both matrices may rise with prolonged storage. Because it is produced as a post-mortem artifact, forensically defensible cut-offs for post-mortem blood concentrations have yet to be established. Given the enormous degree of inter and intra-individual variation in GHB production that has been documented, it is unlikely they ever will. The important issue for forensic scientists is whether the detection of GHB in urine, in concentrations above some yet to be determined value, can be used as evidence for drug facilitated assault. In an attempt to see if a cut-off level could be determined we analyzed urine from 39 alcoholics who were being treated with known oral doses of Alcover (group 1), and compared the results with concentrations found in the urine of 30 volunteers who had no exogenous GHB intake (group 2), and 30 urine specimens taken from the alcoholics before they initiated GHB therapy (Alcover treatment group 3). More than one third (36.6%) of subjects being treated with GHB were found to have urinary GHB concentration that fell between 2.75 and 10 microg/mL. The data suggests that caution must be used when applying the currently used cut-off of 10 microg/mL.

Publication Types: Comparative Study

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19239966&dopt=ExternalLink

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3: Psychiatr Prax. 2009 Oct;36(7):345-7. Epub 2009 Jan 27.

[Gamma-hydroxybutyrat (GHB)-dependence and -withdrawal in the case of previous alcohol dependence]

[Article in German]

Richter C, Romanowski A, Kienast T.

Klinik fur Psychiatrie und Psychotherapie, Charite Campus Mitte, Charite Universitatsmedizin, Berlin. ch.richter@charite.de

OBJECTIVE: gamma-Hydroxybutyrat (GHB) is used medically for narcolepsy and as a narcotic. It is also a rare illegal drug. In this case report the development of a GHB-dependency against the background of a primary alcohol dependency is described. METHODS: Based on established alcohol withdrawal scales (AWSS by Wetterling, CIWA) and neuropsychological testing procedures (CGI, GAF, SKID-II, PISQ, analog-scale for Craving), the initial situation, the development of psychopathological findings, and the course of detoxification were shown. RESULTS/CONCLUSION: The combined detoxication of GHB and alcohol was successfully finished by a reduction schedule of diazepam. Withdrawal-assessment scales for alcohol were helpful, but show limitations for GHB-withdrawal symptoms. The patient suffers, according to ICD-10, from a multiple drug dependence (alcohol, GHB, abstinence from amphetamines). Symptoms of insomnia, major depression, and generalized anxiety disorder can be associated with the use of GHB. Georg Thieme Verlag KG Stuttgart. New York.

Publication Types: Case Reports English Abstract

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=19173170&dopt=ExternalLink

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4: Am J Drug Alcohol Abuse. 2008;34(2):235-6; author reply 237-8.

Are the effects of gamma-hydroxybutyrate (GHB) treatment partly physiological in alcohol dependence?

Ameisen O.

It has been hypothesized that the therapeutic effects of Gamma-hydroxybutyrate (GHB) in alcohol dependence could be related to ethanol-mimicking action of the drug and that GHB could reduce alcohol craving, intake and withdrawal by acting as a "substitute" of the alcohol in the central nervous system. Nevertheless, alcohol being the strongest trigger of craving and intake, it is difficult to ascribe reduction of craving and intake to ethanol-mimicking activity of GHB. I have recently proposed that alcohol/substance dependence could result from a GHB-deficiency-related dysphoric syndrome in which alcohol/substances would be sought to "substitute" for insufficient GHB effect. GHB is the sole identified naturally occurring gamma-aminobutyric acid B (GABA (B)) receptor agonist. Here, I propose that exogenous GHB might in fact "substitute" for deficient endogeneous GHB and represent true substitutive treatment for GHB-deficiency. And that baclofen and GHB could both compensate for deficient effect of the physiological GABA (B) receptor agonist(s).

Publication Types: Comment Letter

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=18293241&dopt=ExternalLink

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5: Alcohol Alcohol. 2007 Sep-Oct;42(5):506. Epub 2007 Aug 1.

Gamma-hydroxybutyrate (GHB)-deficiency in alcohol-dependence?

Ameisen O.

Publication Types: Comment Letter

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=17673481&dopt=ExternalLink

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6: J Clin Psychopharmacol. 2007 Aug;27(4):418.

Use of alcohol during the treatment of alcohol dependence with gamma-hydroxybutyric acid: risk of severe events are avoided by the dose fractioning of the drug.

Caputo F, Stoppo M, Vignoli T, Francini S, Lorenzini F, Bernardi M.

Publication Types: Comment Letter

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=17632241&dopt=ExternalLink

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7: Am J Drug Alcohol Abuse. 2007;33(3):429-38.

High-risk behaviors and hospitalizations among gamma hydroxybutyrate (GHB) users.

Kim SY, Anderson IB, Dyer JE, Barker JC, Blanc PD.

California Poison Control System, Department of Clinical Pharmacy, University of California, San Francisco, CA 94143-1369, USA. susank@calpoison.org

INTRODUCTION: Little is known about behaviors linked to gamma hydroxybutyrate (GHB) morbidity. METHODS: We surveyed 131 GHB users, using logistic regression to test the associations between the high risk behaviors and hospital treatment for GHB (26 [20%] of subjects). RESULTS: Increased risk of GHB hospital treatment was associated with: co-ingestion of ethanol (OR 5.2; 95% CI 1.7-16), driving under the influence of GHB (OR 3.2; 95%, CI 1.3-7.8),use of GHB to treat withdrawal symptoms (OR 2.9; 95% CI 1.1-7.9), and co-ingestion of ketamine (OR 2.7; 95% CI 1.1-6.7). CONCLUSION: Targeted prevention activities could focus on selected high-risk behaviors.

Publication Types: Research Support, N.I.H., Extramural

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=17613970&dopt=ExternalLink

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8: Am J Drug Alcohol Abuse. 2007;33(3):379-92.

Gamma-hydroxybutyrate reduces both withdrawal syndrome and hypercortisolism in severe abstinent alcoholics: an open study vs. diazepam.

Nava F, Premi S, Manzato E, Campagnola W, Lucchini A, Gessa GL.

Italian Society of Addiction Medicine FederSerD, Milan, Italy. navaf@ulssasolo.ven.it

In 42 alcoholic inpatients we performed an open randomized study to compare the effects of diazepam and gamma-hydroxybutyrate (GHB) on the suppression of severe alcohol withdrawal syndrome and hypercortisolism. Both diazepam (.5 mg/kg bodyweight, q.i.d.) and GHB (50 mg/kg bodyweight, q.i.d.) were orally administered for three weeks. During all study period, GHB was more able than diazepam in reducing both withdrawal syndrome and hypercortisolism. These effects were evident during the first week of treatment and persisted throughout the study period. The results confirm a strict correlation between high levels of plasma cortisol and alcohol withdrawal symptoms and they show a slight superiority of GHB over diazepam in the suppression of both ethanol withdrawal and hypercortisolism. Taken together, our data suggest that GHB may act as potent anti-withdrawal agent in severe abstinent alcoholics.

Publication Types: Comparative Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=17613965&dopt=ExternalLink

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9: Eur Neuropsychopharmacol. 2007 Dec;17(12):781-9. Epub 2007 Jul 3.

Comparing and combining gamma-hydroxybutyric acid (GHB) and naltrexone in maintaining abstinence from alcohol: an open randomised comparative study.

Caputo F, Addolorato G, Stoppo M, Francini S, Vignoli T, Lorenzini F, Del Re A, Comaschi C, Andreone P, Trevisani F, Bernardi M, Alcohol Treatment Study Group.

G. Fontana Centre for the Study and Multidisciplinary Treatment of Alcohol Addiction, Department of Internal Medicine, Cardioangiology and Hepatology, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy. fabio-caputo@libero.it

Maintaining abstinence from alcohol is the main goal in treating alcohol dependence. Our aim was to evaluate the efficacy of gamma-hydroxybutyric acid (GHB) and naltrexone (NTX), and their combination in maintaining abstinence. Fifty-five alcoholics were randomly enrolled in three groups and treated for 3 months with GHB, GHB plus NTX, and NTX, respectively. At the end of treatments, abstinence was maintained by 13 patients (72.2%) in combination group, 8 patients (40%; P=0.03) in GHB group, and one patient (5.9%; P=0.0001) in NTX group. Relapses in heavy drinking tended to occur more frequently in GHB group (15%) than in either combination group (no cases) or NTX group (5.9%), but such differences were not statistically significant. The GHB/NTX combination was more effective than either drug given alone; this suggests that the two drugs combine their different actions synergistically without suppressing the favourable effects of each other.

Publication Types: Clinical Trial Comparative Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=17611081&dopt=ExternalLink

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10: J Psychoactive Drugs. 2006 Sep;38(3):211-7.

Comparing treatments of alcoholism on craving and biochemical measures of alcohol consumptionst.

Nava F, Premi S, Manzato E, Lucchini A.

Department of Addiction Medicine, Drug Abuse Unit (Ser.T.), Hospital of Castelfranco Veneto, Via Ospedale, 18, 31033 Castelfranco Veneto-Treviso, Italy. felnava@tin.it

An open randomized study was conducted to compare different treatments of alcoholism on ethanol intake, craving, and on biochemical measures of alcohol consumptions. Eighty-six alcoholics were abstinent for a mean of two weeks prior to random assignment to g-hydroxybutyrate (GHB, 50 mg/kg of body weight t.i.d), naltrexone (NTX, 50 mg/day) or disulfiram (DSF, 200 mg/ day) treatment for 12 months. All treatments were equally effective in reducing alcohol intake and in maintaining abstinence. In all patients, the treatments were able to reduce both craving and the altered biological markers of alcohol abuse. The maximum effects were observed in GHB-treated patients. The results of the present study suggest that GHB might act both as anticraving and cellular protector agent.

Publication Types: Comparative Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=17165363&dopt=ExternalLink

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11: Lancet. 2005 Sep 17-23;366(9490):981-2.

Gamma-hydroxybutyrate as a treatment for alcoholism.

Caputo F, Addolorato G, Trevisani F, Bernardi M.

Publication Types: Comment Letter

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=16168773&dopt=ExternalLink

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12: Drug Alcohol Depend. 2006 Feb 28;81(3):323-6. Epub 2005 Sep 6.

Clinical features of gamma-hydroxybutyrate and gamma-butyrolactone toxicity and concomitant drug and alcohol use.

Liechti ME, Kunz I, Greminger P, Speich R, Kupferschmidt H.

Department of Internal Medicine, University Hospital of Zurich, Zurich, Switzerland. meliechti@dplanet.ch

OBJECTIVE: To describe the clinical features of gamma-hydroxybutyrate (GHB) and gamma-butyrolactone (GBL) toxicity. METHODS: Retrospective case-study of 65 GHB and GBL intoxications seen in an urban emergency department. RESULTS: 63% of intoxications occurred in male patients. The median age was 24 years (range 16-41 years). 65% co-ingested alcohol or illicit drugs, mostly MDMA and cocaine. 83% presented with coma. The mean+/-S.D. time to regain consciousness among comatose patients was 111+/-61 min and was significantly longer in patients who co-abused illicit drugs such as cocaine or MDMA (155+/-60 min). Bradycardia occurred in 38%, hypotension in 6% and hypothermia in 48%. Agitation was observed in 17% of all patients and was significantly more frequent in patients with alcohol co-use (29%). Vomiting occurred in 31% of all patients and tended to be more frequent in patients who co-used alcohol (39%). Management of GHB and GBL overdose was supportive. Four patients needed admission to an intensive care unit for mechanical ventilation (6%). CONCLUSIONS: Overdosing of GHB and GBL frequently results in non-reactive coma reflecting the severity of poisoning. Multiple drug use is common and significantly influences the clinical presentation.

Publication Types: Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=16143455&dopt=ExternalLink

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13: Nervenarzt. 2005 Jul;76(7):832, 834-8.

[Gamma-hydroxybutyrate--a neurotransmitter, medicine, and drug]

[Article in German]

Trendelenburg G, Strohle A.

Neurologische Klinik und Poliklinik, Charite Campus Mitte, Charite Universitatsmedizin Berlin, Schumannstrasse. george.trendelenburg@charite.de

Gamma-hydroxybutyrate (GHB) is a short fatty acid and physiologic neurotransmitter. Initially, it was synthesized as a GABA agonist and used as a narcotic agent, because it rapidly induces sleep without major cardiovascular or respiratory side effects. Recently, a specific GHB receptor was identified, but while the clinical use of GHB as an anaesthetic was reduced due to putative pro-convulsive effects, it now is used to treat alcohol withdrawal and sleep disorders. Furthermore, GHB was postulated to be a regulator of energy metabolism, and tissue-protective effects were demonstrated in different animal models. Besides its clinical use, GHB (also called "liquid ecstasy") is increasingly consumed in the disco scene because of its mild sedative and euphoric effects. Intoxication from GHB is common with GHB users. For this reason and because GHB is not easy to detect, it is important to be aware of the symptoms of GHB intoxication. Moreover, some recent case reports document the danger of GHB dependence.

Publication Types: English Abstract Review

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=15580464&dopt=ExternalLink

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14: Acad Emerg Med. 2003 Jan;10(1):95-6; author reply 96.

Unsupported "Efficacy" claims of gamma hydroxybutyrate (GHB).

Zvosec DL, Smith SW.

Publication Types: Comment Letter

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=12511324&dopt=ExternalLink

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15: South Med J. 2002 Aug;95(8):926-8.

Self-medication with gamma-hydroxybutyrate to reduce alcohol intake.

Glisson JK, Norton J.

Department of Neurology and Psychiatry, University of Mississippi Medical Center, Jackson, USA.

We describe a 52-year-old man who self-medicated with gamma-hydroxybutyrate (GHB), a widely available illicit substance, to obtain a decrease in ethanol consumption. He successfully reduced his ethanol intake over a 3-month period, but he was unable to sustain abstinence. Although case reports on the use of GHB to induce euphoria have been published, this is the first report of GHB self-medication to facilitate ethanol abstinence. This report highlights the importance of considering GHB self-medication not only for euphoric and mood altering effects, but also as a potential treatment for ethanol intake reduction.

Publication Types: Case Reports

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=12190234&dopt=ExternalLink

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16: Alcohol Alcohol. 2002 Jan-Feb;37(1):67-73.

Double-blind controlled trial of gamma-hydroxybutyrate and clomethiazole in the treatment of alcohol withdrawal.

Nimmerrichter AA, Walter H, Gutierrez-Lobos KE, Lesch OM.

Anton-Proksch-Institute Vienna, Dominikanerbastei 21/49, A-1010 Vienna, Austria.

The aim of this double-blind, comparative study was to assess the efficacy and safety of gamma-hydroxybutyrate (GHB) in ameliorating the symptoms of alcohol withdrawal. Newly admitted alcohol-dependent patients (n = 98) were randomized to receive either clomethiazole 1000 mg daily (CLO group) (n = 33), or 50 mg GHB/kg body wt (n = 33) or 100 mg GHB/kg body wt (n = 32). This dose was administered for 5 days, halved on day 6, and on days 7 and 8 only placebo was given. As CLO is available as capsules and GHB as syrup, a double-dummy method was used to try to ensure blindness. The groups were matched in terms of baseline demographic and alcohol-related variables. There was no difference between the three treatments in ratings of alcohol withdrawal symptoms nor requests for additional medication. After tapering off the active medication, there was no increase in withdrawal symptoms, indicating that physical tolerance did not develop to either GHB or CLO within the 5-day treatment period. The most frequently reported side-effect of GHB was transient vertigo, particularly after the evening double dose.

Publication Types: Clinical Trial Comparative Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=11825860&dopt=ExternalLink

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17: J Psychoactive Drugs. 2001 Apr-Jun;33(2):135-42.

Long-term therapy using GHB (sodium gamma hydroxybutyrate) for treatment-resistant chronic alcoholics.

Maremmani I, Lamanna F, Tagliamonte A.

Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, University of Pisa, Italy.

Thirty-five alcohol-dependent patients according to DSM-IV criteria who also met criteria for treatment resistance were treated with doses of gamma hydroxybutyrate (GHB) ranging between 25 and 100 mg/kg/die in an open one-year study. The results show that no patients discontinued the program during the first month of treatment. Sixty percent of these patients successfully completed the protocol; 11.4% showed complete abstinence (full responder patients); 14.3% strongly reduced their alcohol intake (partial responder patients) and 34.3% of the patients were still under treatment after one year. Forty percent of the patients were nonresponders. The retention rate under treatment of the studied sample was statistically higher than that found during the last treatment of the same subjects. No significant differences were found between full responder and partial responder patients regarding changes in clinical features, alcohol intake or social adjustment. Patients still in treatment after one year significantly differed from nonresponder patients on all the variables investigated. A six-times/daily fractionated administration of the GHB dose was the only significant predictor of the retention rate.

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=11476260&dopt=ExternalLink

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18: Thromb Res. 2001 May 1;102(3):255-60.

Effect of gamma-hydroxybutyric acid on human platelet aggregation in vitro.

Franconi F, Miceli M, Alberti L, Boatto G, Coinu R, De Montis MG, Tagliamonte A.

Department of Pharmacology, University of Sassari, Sassari, Italy. franconi@ssmain.uniss.it

Publication Types: Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=11369419&dopt=ExternalLink

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19: Am J Addict. 2001;10 Suppl:3-15.

New developments in the pharmacotherapy of alcohol dependence.

Myrick H, Brady KT, Malcolm R.

Department of Psychiatry, Medical University of South Carolina, 67 President Street, P.O. Box 250861, Charleston, SC 29425, USA. myrickh@musc.edu

Neuroscientific underpinnings and pharmacotherapeutic treatments of substance use disorders are rapidly developing areas of study. In particular, there have been exciting new developments in our understanding of the involvement of excitatory amino acid neurotransmitter systems and the opiate and serotonin systems in the pathophysiology of alcohol withdrawal, alcohol dependence, and in subtypes of individuals with alcoholism. In this article, new developments in the pharmacotherapy of alcohol dependence will be reviewed. In particular, the use of anticonvulsants in alcohol withdrawal and protracted abstinence syndromes will be discussed. New data on opiate antagonists and acamprosate, an agent that exerts actions through excitatory amino acid systems in relapse prevention, will be reviewed. Finally, there will be a review of new data concerning the use of serotonin reuptake inhibitors in subtypes of alcoholism and the use of combination pharmacotherapy.

Publication Types: Review

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=11268820&dopt=ExternalLink

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20: J Emerg Nurs. 2000 Dec;26(6):544-8.

A 30-year-old woman with possible unknown ingestion of date rape drugs.

Kronz CS.

Emergency Department, Arlington Hospital, Arlington, Va, USA. cynthia.kronz@gte.net

Publication Types: Case Reports

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=11106451&dopt=ExternalLink

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21: Emerg Med Clin North Am. 2000 May;18(2):273-88.

Withdrawal syndromes.

Olmedo R, Hoffman RS.

New York City Poison Control Center, New York, USA.

The pathophysiology of substance withdrawal is elucidated by a review of classic and cutting-edge research. The manifestation and evaluation of the associated withdrawal syndromes from ethanol, sedative-hypnotics, opioids, and baclofen, are compared. The general management of and pharmacotherapy for these patients are discussed.

Publication Types: Review

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=10767884&dopt=ExternalLink

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22: Lancet. 1998 Jan 3;351(9095):38.

Maintaining abstinence from alcohol with gamma-hydroxybutyric acid.

Addolorato G, Cibin M, Capristo E, Beghe F, Gessa G, Stefanini GF, Gasbarrini G.

Publication Types: Clinical Trial Letter Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=9433435&dopt=ExternalLink

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23: Addiction. 1997 Aug;92(8):1035-6.

gamma-Hydroxybutyric acid in the treatment of alcohol dependence: possible craving development for the drug.

Addolorato G, Caputo F, Stefanini GF, Gasbarrini G.

Publication Types: Comment Letter Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=9376774&dopt=ExternalLink

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24: Alcohol Clin Exp Res. 1997 Apr;21(2):380.

Manageability and tolerability of gamma-hydroxybutyric acid in the medium term outpatient treatment of alcoholism.

Addolorato G, Stefanini GF, Gasbarrini G.

Publication Types: Comment Letter Multicenter Study

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=9113279&dopt=ExternalLink

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25: Alcohol Alcohol. 1997 Jan-Feb;32(1):85-90.

Persistence of defective serotonergic and GABAergic controls of growth hormone secretion in long-term abstinent alcoholics.

Vescovi PP, Coiro V.

Centre for Alcohology, University of Parma, Italy.

In order to establish whether long-term abstinence from alcohol reverses the defective serotonergic and GABAergic controls of growth hormone (GH) secretion affecting alcoholic patients, the 5-HT1D serotonergic receptor agonist sumatriptan and the GABAergic agent gamma-hydroxybutyric acid (GHB) were administered to 12 normal men (32-49 years) and 22 non-depressed male alcoholic subjects (38-52 years) after 1-2 years of abstinence from alcohol. All subjects were also tested with placebos. Furthermore, tests with GH-releasing hormone (GHRH) and L-arginine (which releases GH from somatostatin inhibition) were performed to determine whether GH secretion in response to its major determinants is preserved in alcoholics. Administration of placebo did not change plasma GH levels in any subject. Similar GH responses were observed in normal controls and alcoholic subjects when GHRH or arginine were administered. A significant GH increase was observed in normal controls after sumatriptan or GHB injection; in contrast, GH secretion was not modified by sumatriptan or GHB administration in alcoholic patients. These data show a persistent selective loss of 5-HT1D receptor and GHB-mediated neurotransmissions in alcoholics that a long-term abstinence from alcohol is unable to restore.

Publication Types: Clinical Trial Controlled Clinical Trial

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=9131896&dopt=ExternalLink

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26: Neurology. 1996 Nov;47(5):1351.

Grievous bodily harm.

Carrazana EJ.

Publication Types: Comment Letter

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=8909463&dopt=ExternalLink

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27: Alcohol Alcohol. 1996 Jul;31(4):341-5.

An open multicentric study evaluating 4-hydroxybutyric acid sodium salt in the medium-term treatment of 179 alcohol dependent subjects. GHB Study Group.

Addolorato G, Castelli E, Stefanini GF, Casella G, Caputo F, Marsigli L, Bernardi M, Gasbarrini G.

Internal Medicine II Chair, Catholic University Sacro Cuore, Rome, Italy.

We report the results of an "open' multicentre study evaluating the use, tolerability and therapeutic efficacy of the sodium salt of 4-hydroxybutyric acid (GHB) for the medium-term treatment of withdrawal symptoms in 179 patients with alcohol dependence followed up as outpatients. The follow-up of patients was 6 and 12 months after drug discontinuation. Following a daily oral administration of 50 mg/kg for approximately 6 months, no serious systemic or single-organ consequences leading to drug discontinuation were reported, and tolerability was fair in all patients. Eleven subjects (10.1%) showed craving for the drug and voluntarily increased their doses (6-7 times the recommended levels). GHB led to complete abstinence during drug administration in 78.0% of the patients. A significant reduction of compulsive desire ("craving') was observed in parallel, as deduced from evaluation of a specific questionnaire, the Alcohol Craving Scale. At follow-up examination, 43 of the treated subjects remained abstinent at 6 months, and 30 subjects were abstinent for 1 year after drug discontinuation.

Publication Types: Multicenter Study Research Support, Non-U.S. Gov't

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=8879280&dopt=ExternalLink

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28: Neurology. 1996 Feb;46(2):469-71.

"Grievous bodily harm:" gamma hydroxybutyrate abuse leading to a Wernicke-Korsakoff syndrome.

Friedman J, Westlake R, Furman M.

Department of Clinical Neurosciences, Roger Williams Medical Center, Providence, RI 02908, USA.

Gamma-hydroxybutyrate (GHB) is a naturally occurring GABA-like drug used illicitly by bodybuilders. Although there are reports of several cases of GHB abuse, with a variety of nervous system complications, we present the first case associated with a Wernicke-Korsakoff syndrome.

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29: J Pharm Biomed Anal. 1993 Jun;11(6):483-7.

Therapeutic gamma-hydroxybutyric acid monitoring in plasma and urine by gas chromatography-mass spectrometry.

Ferrara SD, Tedeschi L, Frison G, Castagna F, Gallimberti L, Giorgetti R, Gessa GL, Palatini P.

Centre of Behavioural and Forensic Toxicology, University of Padova, Italy.

A gas chromatographic-mass spectrometric (GC-MS) method for the determination of therapeutic levels of gamma-hydroxybutyric acid (GHB) in plasma and urine samples is described. GHB is converted to its lactonic form gamma-butyrolactone (GBL) which is extracted from biological fluids after the addition of the internal standard delta-valerolactone. Final GC-MS analysis is obtained under electron impact selected ion monitoring (SIM) conditions. Mean relative recoveries of GHB from plasma and urine are 75.5% (RSD% = 2.2) and 76.4% (RSD% = 2.4), respectively. The assay is linear over a plasma GHB range of 2-200 micrograms ml-1 (r = 0.999) and a urine GHB range of 2-150 micrograms ml-1 (r = 0.998). Intra- and inter-assay relative standard deviations (n = 5) determined at 10 and 100 micrograms ml-1 are below 5%. The method is simple, specific and accurate, and may be applied for analytical purposes related to pharmacokinetic studies and therapeutic drug monitoring.

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30: Br J Clin Pharmacol. 1992 Sep;34(3):231-5.

Pharmacokinetics of gamma-hydroxybutyric acid in alcohol dependent patients after single and repeated oral doses.

Ferrara SD, Zotti S, Tedeschi L, Frison G, Castagna F, Gallimberti L, Gessa GL, Palatini P.

Centre of Behavioural and Forensic Toxicology, University of Padova, Italy.

1. The pharmacokinetics of gamma-hydroxybutyric acid (GHB) were studied in 10 alcohol dependent subjects after single and repeated therapeutic oral doses (25 mg kg-1 every 12 h for 7 days). 2. GHB was readily absorbed and rapidly eliminated (tmax = 20-45 min; mean t1/2z 27 +/- 5 s.d. min). Urinary recovery of unchanged GHB was negligible (less than 1% of the dose). gamma-butyrolactone was not detected in either plasma or urine, indicating that lactonization of GHB does not occur in vivo. 3. The multiple-dose regimen resulted neither in accumulation of GHB nor in time-dependent modification of its pharmacokinetics. 4. In five subjects, the data were consistent with nonlinear elimination kinetics of GHB. Administration of a 50 mg kg-1 dose to these subjects resulted in significant increases in dose-normalized AUC, t1/2z and mean residence time. 5. Doubling of the dose also resulted in a significant increase in tmax with little change in Cmax. 6. At the administered doses, GHB did not accumulate in the plasma and caused no serious side effects.

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31: Alcohol Clin Exp Res. 1992 Aug;16(4):673-6.

gamma-Hydroxybutyric acid in the treatment of alcohol dependence: a double-blind study.

Gallimberti L, Ferri M, Ferrara SD, Fadda F, Gessa GL.

Addiction Medicine Unit, USSL 21, Padova, Italy.

The effect of gamma-hydroxybutyric acid on alcohol consumption and alcohol craving in alcoholics was investigated in a randomized double-blind study versus placebo. Patients were treated as outpatients during a three month period either with gamma-hydroxybutyric acid (50 mg/kg/day, divided into three daily doses) or with placebo. Of the 82 alcoholics that entered the study, 71 completed it, 36 in the gamma-hydroxybutyric acid and 35 in the placebo group. Alcohol consumption was assessed by the subject's self report. At the 3rd month of treatment, 11 patients in the gamma-hydroxybutyric acid group referred to be abstinent and 15 referred controlled drinking; while in the placebo group only two and six patients referred abstinence and controlled drinking, respectively. Serum-gammaglutamyl-transferase activity correlated with the admitted alcohol consumption. Gamma-hydroxybutyric acid treatment decreased alcohol craving during the 3 months of treatment. Transient side effects were noted by six patients on gamma-hydroxybutyric acid and two on placebo. The results suggest that gamma-hydroxybutyric acid may be useful in the treatment of alcohol dependence.

Publication Types: Clinical Trial Randomized Controlled Trial

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32: Adv Biochem Psychopharmacol. 1992;47:281-8.

Suppression of voluntary alcohol intake in rats and alcoholics by gamma-hydroxybutyric acid: a non-GABAergic mechanism.

Biggio G, Cibin M, Diana M, Fadda F, Ferrara SD, Gallimberti L, Gessa GL, Mereu GP, Rossetti ZL, Serra M.

B. Loddo Department of Experimental Biology, University of Cagliari, Italy.

Publication Types: Clinical Trial Research Support, Non-U.S. Gov't Review

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33: Clin Neuropharmacol. 1992;15 Suppl 1 Pt A:303A-304A.

Gamma-hydroxybutyric acid in the treatment of alcohol dependence.

Gessa GL, Gallimberti L.

Bernard B. Brodie Department of Neuroscience, University of Cagliari, Italy.

Publication Types: Clinical Trial Randomized Controlled Trial

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34: Farmakol Toksikol. 1991 Jan-Feb;54(1):62-4.

[A behavioral and biochemical analysis of the therapeutic effect of sodium oxybutyrate in alcoholic encephalopathy in progeny]

[Article in Russian]

Trofimov SS, Ostrovskaia RU, Smol'nikova NM, Nemova EP, Bobrova OV, Koltovaia NA, Ushakov AN, Tsirenina ML.

The alcoholization of pregnant female rats (5 g/kg) results in a decrease of endogenous ethanol level in their offspring and distant disturbances of the conditioned reflex activities of the young rats deteriorating the formation and preservation of the skill with an emotional positive reinforcement. Sodium gamma-gydroxybutyrate administered in a dose of 50 mg/kg from the 8th to the 20th day of life prevents the above-mentioned disturbances of learning and memory, restores the level of endogenous ethanol, corrects the parameters of lipid and mediator metabolism in the brain and blood changed by prenatal alcoholization.

Publication Types: Comparative Study English Abstract

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35: Biull Eksp Biol Med. 1989 Jul;108(7):62-4.

[Effects of sodium oxybutyrate on the level of catecholamines and serotonin and monoamine oxidase activity in patients with alcoholism]

[Article in Russian]

Treskov VG, Krashkina II, Tsirenina ML, Koltovaia NA, Nikol'skaia GV, Baturin AK, Gapparov MM, Mel'nik EI, Maiskii AI.

Sodium salt of gamma-hydroxybutyric acid (Na-GHB) was administered to 37 drug-free alcoholic men in placebo controlled study. The psychotropic effect was evaluated using psychometric scale of 4 ranges. Changes in plasma levels of epinephrine, norepinephrine, dopamine, serotonin and platelet MAO-B activity were assessed. The psychotropic effect was observed in 27 (76%) patients. The baseline of dopamine concentration was significantly correlated with the expression of psychotropic effect. Na-GHB decreased dopamine concentration in responders. The possible involvement of dopaminergic system in the realization of psychotropic effect of Na-GHB was discussed.

Publication Types: Comparative Study English Abstract

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36: Farmakol Toksikol. 1988 May-Jun;51(3):89-94.

[Sodium oxybutyrate correction of the disorders in higher nervous activity in the progeny of alcoholized animals]

[Article in Russian]

Ostrovskaia RU, Smol'nikova NM, Savchenko NM, Trofimov SS, Nemova EP.

Alcoholization of female rats before pregnancy (8 g/kg) or during pregnancy (4 g/kg) leads to disturbances in the development of the offspring higher nervous activity manifested by impaired learning abilities, disordered emotional reactivity, reduced capacity to overcome stress-situation, deficit of GABAergic inhibitory processes in the cerebral cortex. An early postnatal administration of sodium hydroxybutyrate in a dose of 50 mg/kg prevents the development of the above mentioned disturbances of the higher nervous activity and neurophysiological alterations.

Publication Types: Comparative Study English Abstract

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37: Subst Alcohol Actions Misuse. 1984;5(5):263-71.

Effect of ethanol and acetaldehyde on gamma-hydroxybutyric acid in rat brain and liver.

Poldrugo F, Snead OC 3rd.

We examined the effect of acute and chronic ethanol administration on brain and liver gamma-hydroxybutyric acid (GHB), the effect of pyrazole on the ethanol-GHB interaction, and the effect of acetaldehyde on brain and liver GHB. Ethanol produced a marked increase in liver GHB but had no effect on GHB in brain. The ethanol effect in liver was not blocked by pyrazole. Acetaldehyde had no effect in brain or liver on GHB.

Publication Types: Research Support, U.S. Gov't, P.H.S.

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38: Sov Med. 1984;(12):67-71.

[Hemosorption in narcologic practice]

[Article in Russian]

Churkin EA, Gegenava NO.

Publication Types: Review

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39: Biull Eksp Biol Med. 1983 Jan;95(1):60-2.

[Effect of tranquilizing agents on the blood level of endogenous ethanol in alcoholics]

[Article in Russian]

Burov IuV, Treskov VG, Drozdov ES, Kovalenko AE.

Experiments on alcohol addicts blood were made to study the time course of the endogenous ethanol level after a single administration of mebicar (1.5 g), a derivative of bicyclic bisuria, 50 ml of 5% sodium hydroxybutyric syrup, a derivative of gamma-hydroxybutyric acid, and 20 mg diazepam, a derivative of 1,4-benzodiazepines. The clinical effect was recorded simultaneously. It was established that different tranquilizers stimulate the increase in the endogenous ethanol level as regards the spectrum of psychotropic activity. This effect was the most pronounced with mebicar and to a less measure with diazepam.

Publication Types: English Abstract

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40: Int J Addict. 1981 Aug;16(6):1071-5.

Circadian rhythm in plasma concentrations of gamma-hydroxybutyric acid in alcoholics.

Hoes MJ, Vree TB, Guelen PJ.

Gamma-hydroxybutyric acid (GHB) was orally administered to six alcoholics at 09.00 and 23.00 h. The plasma concentrations of GHB show a clear circadian pattern, the area under the curve in the daytime experiments being 61% of that in the night experiments. The significance of alcohol dehydrogenase, the catabolic enzyme of GHB, for the difference is discussed. It is concluded that, although the activity of alcohol dehydrogenase in alcoholics is quantitatively disturbed, it remains subject to physiologic circadian activation.

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41: Biull Eksp Biol Med. 1981 Jun;91(6):689-91.

[Effect of psychotropic drugs on sleep disorders in rats during alcohol withdrawal]

[Article in Russian]

Burov IuV, Viglinskaia IV.

The effects of sodium hydroxybutyrate (100 mg/kg); phenazepam (1 mg/kg), apomorphine (0.1 mg/kg and haloperidol (1 mg/kg) on the electrophysiological sleep pattern were studied in rats during 7-day alcohol withdrawal after its voluntary consumption for 13 months. It was shown that alcohol withdrawal led to profound disorders in the sleep-waking cycle. Sodium hydroxybutyrate prevented these disturbances and brought sleep to normal. Phenazepam exerted a powerful sedative and hypnotic effects but did not improve the balance of sleep phases. Apomorphine displayed a tendency to sleep normalization. However, this effect was short-term. Haloperidol did not eliminate abstinence manifestations in the sleep pattern.

Publication Types: English Abstract

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42: Zh Nevropatol Psikhiatr Im S S Korsakova. 1981;81(7):1064-7.

[Prolonged pharmacologic sleep in the complex treatment of patients with severe forms of alcoholic delirium]

[Article in Russian]

Danilenko AM, Veselovskii VV, Kuznetsov VI, Vorobeichik GN, Tuz MV.

Results of treating 235 patients suffering from grave alcohol delirium complicated with somatic pathology are presented. Use was made of various methods of inducing prolonged drug sleep: by neuroleptics, barbiturates with analgesics sodium gamma-hydroxybutyrate alone or in combination with barbiturates or viadril. The method of using the combination of sodium gamma-hydroxybutyrate with barbiturates or viadril G appeared to be the most effective. It use resulted in a rapid elimination of psychomotor excitation, quick induction of deep sleep, considerable shortening of the psychotic period, rapid normalization of vitally important body functions, and shortening of the duration of the post-delirium asthenization.

Publication Types: English Abstract

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43: Zh Nevropatol Psikhiatr Im S S Korsakova. 1980;80(1):130-1.

[Hemosorption and the treatment of alcoholic delirium]

[Article in Russian]

Obukhov GA.

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44: Farmakol Toksikol. 1978 Nov-Dec;41(6):660-5.

[Effect of several psychotropic agents on changes in the behavior of mice induced by acetaldehyde]

[Article in Russian]

Andronova LM, Barkov NK, Vikhliaev IuI.

Results of a study on the effect produced by 26 psychotropic agents on a complex set of behavioral changes in mice induced by introduction of acetaldehyde are presented. Experiments were conducted according to the method of Ortiz et al. (1973) who have proposed this test as a model of the abstinence syndrome. The effect of the agents was evaluated by removal of convulsions according to the Goldstein 4-point scale system (1972). In this respect the most effective proved tranquilizers, hypnotics, sodium oxybutyrate and ethanol. Little effective were neuroleptics and antidepressants. The model may be used in the screening of drugs when treating the abstinence syndromes in chronic alcoholism.

Publication Types: English Abstract

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45: Sov Med. 1977 Jul;(7):47-51.

[Treatment of alcoholic psychoses]

[Article in Russian]

Sokolova EP, Begunov VI.

Publication Types: English Abstract

Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=897809&dopt=ExternalLink

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MedASq (the Medline Abstract Squeezer) is © Ernesto de Bernardis 2002. Thanks to Eric Mueller for his on-the-fly ZIP creation code, to Google for automatic translations, to the NCBI people who wrote the new Entrez Utilities, and to the USA Government and NLM who allowed free access to the PubMed database [Disclaimer]. The URL of this site is http://www.debernardis.it/medasq.php; my home page is in http://www.debernardis.it