sodium-oxybate and Alcoholism

The estimated effect of sodium oxybate (SMO) in the treatment of alcohol dependence is heterogeneous. Population severity and treatment duration have been identified as potential effect modifiers. Population severity distinguishes heavy drinking patients with <14 days of abstinence before treatment initiation (high-severity population) from other patients (mild-severity population). Treatment duration reflects the planned treatment duration. This study aimed to systematically investigate the effect of these potential effect moderators on SMO efficacy in alcohol-dependent patients.. Network meta-regression allows for testing potential effect modifiers. It was selected to investigate the effect of the above factors on SMO efficacy defined as continuous abstinence (abstinence rate) and the percentage of days abstinent (PDA). Randomized controlled trials for alcohol dependence with at least one SMO group conducted in high-severity and mild-severity populations were assigned to a high-severity and mild-severity group of studies, respectively.. Eight studies (1082 patients) were retained: four in the high-severity group and four in the mild-severity group. The high-severity group was associated with larger SMO effect sizes than the mild-severity group: abstinence rate risk ratio (RR) 3.16, P = 0.004; PDA +26.9%, P < 0.001. For PDA, longer treatment duration was associated with larger SMO effect size: +11.3% per extra month, P < 0.001. In the high-severity group, SMO showed benefit: abstinence rate RR 2.91, P = 0.03; PDA +16.9%, P < 0.001. In the mild-severity group, SMO showed benefit only in PDA for longer treatment duration: +23.9%, P < 0.001.. In the retained studies with alcohol-dependent patients, high-severity population and longer treatment duration were associated with larger SMO effect sizes.

Topics: Alcoholism; Duration of Therapy; Ethanol; Humans; Regression Analysis; Sodium Oxybate; Treatment Outcome

GHB (gamma-hydroxybutyric acid; sodium oxybate) is a general anaesthetic that is clinically used for the treatment of narcolepsy, cataplexy, alcohol withdrawal and alcohol relapse prevention. In addition, GHB is recreationally used. Most clinical and recreational users regard GHB as an innocent drug devoid of adverse effects, despite its high dependence potential and possible neurotoxic effects. At high doses, GHB may lead to a comatose state. This paper systematically reviews possible cognitive impairments due to clinical and recreational GHB use.. PubMed and PsychINFO were searched for literature data about the acute and residual cognitive deficits following GHB use. This review is conducted using the PRISMA protocol.. A total of 43 reports covering human and animal data on GHB-induced cognitive impairments were eligible and reviewed. This systematic review found no indication for cognitive impairments after clinical GHB use. However, it supports the view that moderate GHB use may result in acute short-term cognitive impairments, whereas regular high-dose GHB use and/or multiple GHB-induced comas are probably neurotoxic resulting in long-term residual cognitive impairments.. These results emphasize the need for awareness among clinicians and recreational users to minimize negative health consequences of recreational GHB use, particularly when high doses are used and GHB-induced comas occur.

Topics: Alcoholism; Animals; Cognitive Dysfunction; Coma; Humans; Hydroxybutyrates; Illicit Drugs; Neurotoxicity Syndromes; Sodium Oxybate; Substance Withdrawal Syndrome

Topics: Alcoholism; Humans; Randomized Controlled Trials as Topic; Sodium Oxybate; Substance Withdrawal Syndrome

Medication development for alcohol relapse prevention or reduction of consumption is highly challenging due to methodological issues of pharmacotherapy trials. Existing approved medications are only modestly effective with many patients failing to benefit from these therapies. Therefore, there is a pressing need for other effective treatments with a different mechanism of action, especially for patients with very high (VH) drinking risk levels (DRL) because this is the most severely affected population of alcohol use disorder patients. Life expectancy of alcohol-dependent patients with a VH DRL is reduced by 22 years compared with the general population and approximately 90 000 alcohol-dependent subjects with a VH DRL die prematurely each year in the EU (Rehm et al. ). A promising new medication for this population is sodium oxybate, a compound that acts on GABA

Topics: Adolescent; Adult; Alcohol Deterrents; Alcoholism; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Secondary Prevention; Sodium Oxybate; Young Adult

The treatment of alcohol use disorder (AUD) with sodium oxybate (SMO) or gamma-hydroxybutyric acid (GHB) was introduced in Italy and Austria more than 20 years and 15 years ago, respectively, and it is now widely employed to treat alcohol withdrawal syndrome (AWS) and to maintain alcohol abstinence. These indications derive from its similar structure to the inhibitory neurotransmitter γ-amino-butyric acid (GABA), exerting an ethanol-mimicking effect, because it binds to GABAB receptors. Craving for, and abuse of, SMO remain a controversial issue; even though these unfavorable effects are evident in poly-drug addicted patients and in those with psychiatric diagnosis of borderline personality disorder. In addition, despite cases of severe intoxication and deaths being widely documented when GHB is used as "street drug"; its clinical use remains safe. Thus, the aim of the present review is to examine the role of SMO in the treatment of AUD, its possible implications in reducing alcohol consumption, and cases of abuse, and severe intoxication due to SMO during its clinical use in the treatment of AUD.

Topics: Adult; Aged; Aged, 80 and over; Alcohol Drinking; Alcohol-Related Disorders; Alcoholism; Austria; Female; Humans; Hydroxybutyrates; Italy; Male; Middle Aged; Sodium Oxybate; Substance Withdrawal Syndrome; Young Adult

Sodium oxybate (SMO) has been shown to be safe and effective in the treatment of patients with alcohol use disorders (AUDs); it was approved in Italy and Austria for the treatment of alcohol withdrawal syndrome and for relapse prevention. The focus of this review is to discuss the clinical evidence on the therapeutic potential of SMO for AUDs.. This review covers the studies in patients with alcohol withdrawal syndrome who received SMO for the treatment of withdrawal symptoms and the studies in patients with AUDs who received SMO to achieve total alcohol abstinence, reduction of alcohol intake, and relapse prevention. Relevant medical literature on SMO was identified by searching databases including MEDLINE and EMBASE (searches last updated 20 September 2013), bibliographies from published literature, clinical trial registries/databases, and websites.. SMO has proved safe and effective in the treatment of alcohol withdrawal syndrome and in the prevention of relapses. Craving for and abuse of SMO have been reported, in particular in some subtypes of alcoholic patients, e.g., those affected by co-addiction and/or psychiatric comorbidity. Future multicenter, multinational, randomized clinical trials should be useful to optimize the treatments in relation with patients' characteristics, for example, pharmacogenetic, neurobiological, and psychological.

Topics: Alcohol Drinking; Alcoholism; Animals; Drug Approval; Humans; Secondary Prevention; Sodium Oxybate; Substance Withdrawal Syndrome; Temperance; Treatment Outcome

A liquid formulation of sodium oxybate (Alcover(®)), the sodium salt of γ-hydroxybutyric acid (GHB), is approved in Italy and Austria for use in alcohol withdrawal syndrome and for the maintenance of abstinence in alcohol dependence. This article reviews the efficacy and tolerability of sodium oxybate in alcohol withdrawal syndrome and in the maintenance of abstinence in alcohol dependence, as well as summarizing its pharmacological properties. Results of randomized controlled trials indicate that sodium oxybate was at least as effective as diazepam and clomethiazole in patients with alcohol withdrawal syndrome, rapidly alleviating symptoms, and was at least as effective as naltrexone or disulfiram in the maintenance of abstinence in alcohol-dependent patients. Sodium oxybate was generally well tolerated. The risk of sodium oxybate abuse is generally low when it is administered to alcohol-dependent patients at its approved dosage, under the supervision of a designated family member and with continuous strict medical surveillance. However, certain patient groups, such as patients with alcohol dependence and borderline personality disorder or who are in remission from heroin or cocaine addiction, may not be suitable candidates for sodium oxybate therapy because of an increased risk of abuse. In conclusion, sodium oxybate is a useful option for the treatment of alcohol withdrawal syndrome and for the maintenance of abstinence in alcohol dependence.

Topics: Alcohol Abstinence; Alcohol Deterrents; Alcohol Drinking; Alcoholism; Animals; Behavior, Addictive; Disease Models, Animal; Drug Interactions; Humans; Sodium Oxybate; Substance Withdrawal Syndrome

Alcohol dependence (AD) is a major public health problem. Currently, three drugs for the treatment of AD have been approved by both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA): acamprosate, disulfiram, and oral naltrexone. The FDA also approved the use of long-acting injectable naltrexone. In Austria and in Italy sodium oxybate is also approved. The EMA's Committee for Medicinal Products for Human Use has recently granted marketing authorization for nalmefene for the reduction of alcohol consumption. Many patients, while accepting the problem, are unable or unwilling to completely stop consuming alcohol, leading to an inevitable deterioration over time of their psycho-physical state, and social and family relationships. It is appropriate to offer these patients the opportunity to significantly reduce their consumption of alcohol. The reduction may be an opportunity to prepare the individual for achieving complete abstinence. Abstinence should always be the main goal. Currently, nalmefene is the only drug that has been authorized for the reduction of alcohol consumption. Its association with psycho-social support is mandatory; it is taken on an "as-needed" basis, which should preferably be 1-2 hours before the possible intake of alcohol. The trials showed a significant reduction in alcohol consumption, which resulted in a significant reduction in morbidity and mortality. Reducing consumption allows a decrease in the progression of numerous alcohol-induced chronic diseases, as well as a reduction in psycho-physical damage, acts of violence, motor vehicle accidents, and accidents at work, which in turn means fewer healthcare costs.

Topics: Acamprosate; Age of Onset; Alcohol Deterrents; Alcohol-Related Disorders; Alcoholism; Binge Drinking; Contraindications; Craving; Disulfiram; Drugs, Investigational; Europe; Humans; Meta-Analysis as Topic; Multicenter Studies as Topic; Naltrexone; Neurotransmitter Agents; Randomized Controlled Trials as Topic; Sodium Oxybate; Taurine

In several countries, including the Netherlands, the use of GHB seems to be rising. GHB is regarded by recreational users as an innocent drug without any side effects. Recently, the number of patients in treatment due to GHB addiction sharply increased. In addition, various studies report incidents following risky GHB use or GHB overdosing. Other sedative drugs, like ketamine and alcohol have been shown to result in unintended neurotoxic harm at the level of memory and cognitive function. As outlined in the present review, GHB and ketamine have a common mode of action, which suggests that GHB may also lead to similar neurotoxicity as ketamine. GHB overdosing, as well as binge drinking (and high ketamine doses), induce profound coma which is probably neurotoxic for the brain especially in the maturing brain of young adults. It is therefore advocated to investigate possible long-term neurotoxic effects in recreational GHB users e.g. by studying the residual effects on cognition and memory.

Topics: Alcoholism; Anesthetics; Anesthetics, Dissociative; Animals; Central Nervous System Depressants; Cognition Disorders; Coma; Drug Overdose; Ethanol; Glutamic Acid; Humans; Illicit Drugs; Ketamine; Neurotoxicity Syndromes; Oxidative Stress; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders; Succinate-Semialdehyde Dehydrogenase

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 Escitalopram versus Escitalopram alone (RR 4.58; 1.28-16.5). For Alcohol Craving Scale results favour GHB versus placebo (WMD -1.90; -2.45 to 1.35) and Disulfiram (WMD -1.40; -1.86 to-0.94).. GHB 50mg is effective compared to placebo in the treatment of AWS, and in preventing relapses in previously detoxified alcoholics at 3 months follow-up, but the results of this review do not provide sufficient evidence in favour of GHB compared to benzodiazepines and Chlormethiazole for AWS prevention. GHB is better than NTX and Disulfiram in maintaining abstinence and it has a better effect on craving than placebo and Disulfiram. Side effects of GHB are not statistically different from those with BZD, NTX or Disulfiram. However, concern has been raised regarding the risk of developing addiction, misuse or abuse, especially in polydrug abusers.

Topics: Alcoholism; Ethanol; Humans; Randomized Controlled Trials as Topic; Secondary Prevention; Sodium Oxybate; Substance Withdrawal Syndrome

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.

Topics: Alcoholism; Animals; Clinical Trials as Topic; Humans; Risk Factors; Sodium Oxybate; Substance-Related Disorders

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.

Topics: Acamprosate; Adjuvants, Anesthesia; Alcohol Deterrents; Alcoholism; Anticonvulsants; Buspirone; Carbamazepine; Drug Therapy; Ethanol; Humans; Naltrexone; Narcotic Antagonists; Randomized Controlled Trials as Topic; Ritanserin; Serotonin Agents; Sodium Oxybate; Substance Withdrawal Syndrome; Taurine; Valproic Acid; Vigabatrin

Topics: Alcohol Drinking; Alcoholism; Animals; gamma-Aminobutyric Acid; Humans; Rats; Sodium Oxybate

Sodium oxybate (SMO) has been shown to be effective in the maintenance of abstinence (MoA) in alcohol-dependent patients in a series of small randomized controlled trials (RCTs). These results needed to be confirmed by a large trial investigating the treatment effect and its sustainability after medication discontinuation.. To confirm the SMO effect on (sustained) MoA in detoxified alcohol-dependent patients.. Large double-blind, randomized, placebo-controlled trial in detoxified adult alcohol-dependent outpatients (80% men) from 11 sites in four European countries. Patients were randomized to 6 months SMO (3.3-3.9 g/day) or placebo followed by a 6-month medication-free period. Primary outcome was the cumulative abstinence duration (CAD) during the 6-month treatment period defined as the number of days with no alcohol use. Secondary outcomes included CAD during the 12-month study period.. Of the 314 alcohol-dependent patients randomized, 154 received SMO and 160 received placebo. Based on the pre-specified fixed-effect two-way analysis of variance including the treatment-by-site interaction, SMO showed efficacy in CAD during the 6-month treatment period: mean difference +43.1 days, 95% confidence interval (17.6-68.5;. Results of this large RCT in alcohol-dependent patients demonstrated a significant and clinically relevant sustained effect of SMO on CAD.. ClinicalTrials.gov Identifier: NCT04648423.

Topics: Adult; Alcohol Drinking; Alcoholism; Double-Blind Method; Ethanol; Female; Humans; Male; Sodium Oxybate; Treatment Outcome

Sodium oxybate (SMO) has been approved in Italy and Austria for the maintenance of abstinence in alcohol dependent (AD) patients. Although SMO is well tolerated in AD patients, cases of abuse and misuse have been reported outside the therapeutic setting. Here we report on a phase IIb double-blind, randomized, placebo-controlled trial for the maintenance of abstinence in AD patients with a new abuse and misuse deterrent formulation of SMO. A total of 509 AD patients were randomized to 12 weeks of placebo or one of four SMO doses (0.75, 1.25, 1.75 or 2.25 g t.i.d.) followed by a one-week medication-free period. The primary endpoint was the percentage of days abstinent (PDA) at end of treatment. An unexpectedly high placebo response (mean 73%, median 92%) was observed. This probably compromised the demonstration of efficacy in the PDA, but several secondary endpoints showed statistically significant improvements. A post-hoc subgroup analysis based on baseline severity showed no improvements in the mild group, but statistically significant improvements in the severe group: PDA: mean difference +15%, Cohen's d = 0.42; abstinence: risk difference +18%, risk ratio = 2.22. No safety concerns were reported. Although the primary endpoint was not significant in the overall population, several secondary endpoints were significant in the intent-to-treat population and post-hoc results showed that treatment with SMO was associated with a significant improvement in severe AD patients which is consistent with previous findings. New trials are warranted that take baseline severity into consideration.

Topics: Alcoholism; Austria; Double-Blind Method; Ethanol; Humans; Sodium Oxybate; Treatment Outcome

Sodium oxybate (SO) is a γ-amino-butyric acid (GABA)-ergic drug currently used for the treatment of alcohol dependence (AD) in some European countries. The aim of this study was to describe the effect of SO administration in alcoholics classified according to Lesch alcoholism typology (LAT). Forty-eight patients were enrolled and classified into four groups according to LAT. All patients were treated with oral SO (50 mg/kg of body weight t.i.d.) for 12 weeks. All patients significantly reduced their alcohol intake (p<0.001). Alcohol abstinence during the 12 weeks of treatment did not differ between the four groups at the end of treatment. Craving for SO did not significantly differ amongst groups; cases of SO abuse were very limited and were observed in almost 10% of patients. In conclusion, our study showed an overall efficacy of SO in the treatment of AD irrespective of LAT categories. However, our results confirm that alcoholics with psychiatric co-morbidity, particularly with a borderline personality disorder of Axis II, are at a greater risk of developing craving for and abuse of the drug: until craving for alcohol and craving for SO are characterized in depth, SO should be used with caution in these patients.

Topics: Adult; Alcohol Abstinence; Alcoholism; Behavior, Addictive; Diagnostic and Statistical Manual of Mental Disorders; Female; GABA Agonists; Humans; Male; Middle Aged; Pilot Projects; Sodium Oxybate; Young Adult

Benzodiazepines (BDZs) are the gold standard in the treatment of alcohol withdrawal syndrome (AWS). Sodium oxybate (SMO) has been tested as a treatment for AWS with encouraging results. The aim of this phase IV, multicenter, randomized, double-blind, double-dummy study was to evaluate the efficacy of SMO in comparison with oxazepam in the treatment of uncomplicated AWS.. Alcohol-dependent outpatients (n = 126) affected by uncomplicated AWS according to the Clinical Institute Withdrawal Assessment for Alcohol-revised (CIWA-Ar) scale were enrolled in the study and randomized in two groups: 61 patients received SMO and 65 patients received oxazepam for 10 days. The primary endpoint was the reduction of symptoms of AWS measured by the change in the total CIWA-Ar score from baseline (day 1) to the end of the study (day 10). This study is registered with ClinicalTrials.gov, number: NCT02090504 RESULTS: A significant decrease of the mean total CIWA-Ar score from baseline to the end of the study was found in both the SMO (p < 0.0001) and the oxazepam group (p < 0.0001), with no significant differences between the two treatments (p = 0.21). Treatment with SMO and oxazepam resulted in a marked decrease in the severity of the mean CIWA subscales, i.e. sweating, tremor, and anxiety, with no significant differences between the two treatments. Both drugs were well tolerated and no severe side effects were reported.. SMO is as effective as oxazepam, one of the gold standard BDZs, in the treatment of uncomplicated AWS. Due to its tolerability and absence of significant side effects, SMO may be considered a valid alternative choice in the treatment of AWS.

Topics: Adult; Alcoholism; Anxiety; Craving; Double-Blind Method; Female; Humans; Male; Oxazepam; Severity of Illness Index; Sodium Oxybate; Substance Withdrawal Syndrome; Surveys and Questionnaires; Sweating; Treatment Outcome; Tremor

Sodium oxybate (SMO) is a GABA-ergic drug currently used for the treatment of alcohol-dependence in some European countries. In particular, clinical studies have shown a role of SMO in promoting alcohol abstinence, as well as in relieving withdrawal symptoms. The aim of this study was to describe alcohol abstinence and the onset of craving for and abuse of SMO in alcohol-dependent subjects with and without psychiatric co-morbidity. Forty-eight patients were enrolled and classified into two groups: group A (20 alcoholics without any psychiatric co-morbidity) and group B (28 alcoholics with a psychiatric co-morbidity). All patients were treated with oral SMO (50 mg/kg of body weight t.i.d.) for 12 weeks. Alcohol abstinence as well as alcohol drinking during the 12 weeks of treatment did not differ between the two groups at the end of treatment (p=0.9). In addition, a reduction of alcohol intake in both groups has been observed (p<0.0001). On the other hand, craving for SMO was significantly more frequent in group B than group A (p=0.001). Cases of SMO abuse were observed in almost 10% of group B patients. In conclusion, alcohol abstinence achieved through SMO administration does not differ in patients with and without psychiatric co-morbidity. However, alcoholics with co-morbid borderline disorders appear to be at high risk of developing craving for and abuse of the drug; therefore, SMO may not be indicated in these patients.

Topics: Alcohol Deterrents; Alcoholics; Alcoholism; Biomarkers, Pharmacological; Comorbidity; Ethanol; Female; GABA Agents; Humans; Male; Mental Disorders; Recurrence; Sodium Oxybate; Substance Withdrawal Syndrome; Temperance; Treatment Outcome

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.

Topics: Adult; Alcoholism; Anesthetics, Intravenous; Drug Therapy, Combination; Evaluation Studies as Topic; Female; Humans; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Sodium Oxybate; Statistics, Nonparametric; Time Factors; Treatment Outcome

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.

Topics: Adult; Alcohol Withdrawal Delirium; Alcoholism; Diazepam; Female; Follow-Up Studies; Humans; Hydrocortisone; Hypnotics and Sedatives; Male; Middle Aged; Sodium Oxybate

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.

Topics: Adult; Alcohol Deterrents; Alcohol Drinking; Alcoholism; Biomarkers; Disulfiram; Female; Humans; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Psychiatric Status Rating Scales; Sodium Oxybate; Temperance

Topics: Adult; Alcohol Deterrents; Alcoholism; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Sodium Oxybate

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.

Topics: Adult; Alcoholism; Double-Blind Method; Female; Follow-Up Studies; Humans; Liver Function Tests; Male; Sodium Oxybate; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome

Topics: Alcoholism; Double-Blind Method; Humans; Sodium Oxybate

Topics: Alcohol Drinking; Alcoholism; Animals; gamma-Aminobutyric Acid; Humans; Rats; Sodium Oxybate

Gamma-hydroxybutyric acid (GHB), both a metabolic precursor and product of gamma-aminobutyric acid (GABA), is a central nervous system depressant used for the treatment of narcolepsy-associated cataplexy and alcohol withdrawal. However, administration of GHB with alcohol (ethanol) is a major cause of hospitalizations related to GHB intoxication. In this study, we investigated locomotor behavior as well as metabolic and pharmacokinetic interactions following co-administration of GHB and ethanol in rats. The locomotor behavior of rats was evaluated following the intraperitoneal administration of GHB (sodium salt, 500 mg/kg) and/or ethanol (2 g/kg). Further, time-course urinary metabolic profiling of GHB and its biomarker metabolites glutamic acid, GABA, succinic acid, 2,4-dihydroxybutyric acid (OH-BA), 3,4-OH-BA, and glycolic acid as well as pharmacokinetic analysis were performed. GHB/ethanol co-administration significantly reduced locomotor activity, compared to the individual administration of GHB or ethanol. The urinary and plasma concentrations of GHB and other target compounds, except for 2,4-OH-BA, were significantly higher in the GHB/ethanol co-administration group than the group administered only GHB. The pharmacokinetic analysis results showed that the co-administration of GHB and ethanol significantly increased the half-life of GHB while the total clearance decreased. Moreover, a comparison of the metabolite-to-parent drug area under the curve ratios demonstrated that the metabolic pathways of GHB, such α- and β-oxidation, were inhibited by ethanol. Consequently, the co-administration of GHB and ethanol aggravated the metabolism and elimination of GHB and enhanced its sedative effect. These findings will contribute to clinical interpretation of GHB intoxication.

Topics: Alcoholism; Animals; Ethanol; gamma-Aminobutyric Acid; Rats; Sodium Oxybate; Substance Withdrawal Syndrome

GHB is a small molecule and is present in the human CNS. Exogenously, GHB is administered orally in the form of sodium oxybate to treat cataplexy and excessive daytime sleepiness in patients with narcolepsy, and to manage alcohol withdrawal and detoxification in alcoholics. GHB shows a biphasic effect and dose-dependent pharmacokinetics and may interact with neuronal systems different from GABAergic one. The compound is also highly abused among bodybuilders and is associated with drugs of abuse.. This article provides an overview of the risks associated with the recreational consumption of GHB and its analogues, including pharmaceuticals mostly encountered in GHB-related emergency department admissions and postmortem investigations. A literature search was performed using PubMed, Scopus, Google Scholar, and Web of Science databases to identify scientific reports concerning the recreational use of GHB and analogs with prescribed drugs. Further articles were retrieved after consulting international health and regulatory authorities' reports.. Due to its dual nature, interpreting and distinguishing GHB concentrations in biological fluid represents a challenge in forensic toxicology. To demonstrate recent exposure, a quick collection of samples is necessary to maximize the chance of detecting an exogenous GHB intake, especially in cases of GHB-facilitated sexual assaults.

Topics: Alcoholism; Drug Interactions; Humans; Sodium Oxybate; Substance Withdrawal Syndrome

COVID-19 has exacerbated income inequality, structural racism, and social isolation-issues that drive addiction and have previously manifested in the epidemic of opioid-associated overdose. The co-existence of these epidemics has necessitated care practice changes, including the use of telehealth-based encounters for the diagnosis and management of opioid use disorder (OUD).. We describe the development of the "Addiction Telehealth Program" (ATP), a telephone-based program to reduce treatment access barriers for people with substance use disorders staying at San Francisco's COVID-19 Isolation and Quarantine (I&Q) sites. Telehealth encounters were documented in the electronic medical record and an internal tracking system for the San Francisco Department of Public Health (SFDPH) COVID-19 Containment Response. Descriptive statistics were collected on a case series of patients initiated on buprenorphine at I&Q sites and indicators of feasibility were measured.. Between April 10 and May 25, 2020, ATP consulted on the management of opioid, alcohol, GHB, marijuana, and stimulant use for 59 I&Q site guests. Twelve patients were identified with untreated OUD and newly prescribed buprenorphine. Of these, all were marginally housed, 67% were Black, and 58% had never previously been prescribed medications for OUD. Four self-directed early discharge from I&Q-1 prior to and 3 after initiating buprenorphine. Of the remaining 8 patients, 7 reported continuing to take buprenorphine at the time of I&Q discharge and 1 discontinued. No patients started on buprenorphine sustained significant adverse effects, required emergency care, or experienced overdose.. ATP demonstrates the feasibility of telephone-based management of OUD among a highly marginalized patient population in San Francisco and supports the implementation of similar programs in areas of the U.S. where access to addiction treatment is limited. Legal changes permitting the prescribing of buprenorphine via telehealth without the requirement of an in-person visit should persist beyond the COVID-19 public health emergency.

Topics: Adult; Alcoholism; Analgesics, Opioid; Buprenorphine; COVID-19; Delivery of Health Care; Feasibility Studies; Female; Health Services Accessibility; Humans; Ill-Housed Persons; Male; Marijuana Abuse; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Public Health; Quarantine; San Francisco; SARS-CoV-2; Sodium Oxybate; Substance-Related Disorders; Telemedicine; Telephone

The causes of high anion gap metabolic acidosis (HAGMA) are well described in the literature. However, sometimes more frequent causes of HAGMA cannot explain its occurrence.In the case of HAGMA and severe neurological depression in the absence of other causes of HAGMA, clinicians should consider an intoxication with gamma-hydroxybutyrate (GHB) as a possible cause.GHB is endogenous to the mammalian central nervous system (CNS). Synthetic GHB was initially used as an anesthetic but is now only licensed for medical use in a limited number of indications such as the treatment of narcolepsy. Because of its euphoric effects, it became popular for recreational use under the street names: Liquid Ecstasy, Georgia Home Boy, and Liquid G.We describe the clinical case of a patient who suffered from severe neurological depression and HAGMA.

Topics: Acidosis; Alcoholism; Gas Chromatography-Mass Spectrometry; Glasgow Coma Scale; Humans; Male; Middle Aged; Narcotics; Sodium Oxybate

Topics: Alcoholism; Animals; Central Nervous System Agents; Humans; Illicit Drugs; Narcolepsy; Sodium Oxybate; Toxicology

The treatment of alcohol use disorder still remains a challenge. The efficacy of the combined pharmacological treatment for alcohol use disorder has been widely investigated with controversial results. The aim of our case series was to investigate the effect of nalmefene in patients not responding to sodium oxybate therapy. We describe seven cases of consecutive patients affected by alcohol use disorder, and treated with sodium oxybate (50 mg/kg per day) who did not achieve complete alcohol abstinence after at least one month of pharmacological treatment. Then, in partial- and non-responder patients to sodium oxybate treatment, administration of nalmefene, 18 mg as needed, was commenced. Our data show that, during the first month of the combined treatment of sodium oxybate plus nalmefene, patients were able to achieve alcohol abstinence (two patients), to suppress (five cases) or reduce (two patients) episodes of heavy drinking days, and to suppress the onset of craving for sodium oxybate (one patient). Likely, nalmefene may act in modulating the excessive reward effect of sodium oxybate, which may be responsible for the persistence of alcohol intake and for the onset of craving for sodium oxybate. However, controlled clinical trials to confirm the safety and efficacy of sodium oxybate plus nalmefene in treating alcohol use disorder are warranted.

Topics: Adult; Alcohol Abstinence; Alcohol Drinking; Alcohol-Related Disorders; Alcoholism; Alcohols; Craving; Female; Humans; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Sodium Oxybate; Treatment Outcome

The treatment of alcohol dependence (AD) with sodium oxybate (SMO) was introduced in Italy and Austria more than 20 years and 15 years ago respectively, and it is now widely employed. In addition to the data obtained from clinical trials, little information is available on specific clinical practices. Thus, the aim of this study was to present and discuss the results of a consensus meeting held after twenty years of using SMO in clinical practice in Italy.. A validated questionnaire study was conducted to investigate the modalities of treatment of AD with SMO currently used in Italy. A group of four referees first drew up the questionnaire which was distributed to fifty experts in the field of alcohol use disorders. The questionnaire consisted of 125 items with five different modalities of response and two or three answer possibilities.. The results of this survey showed a broad consensus on some issues regarding, for example, the duration of treatment, and the dose regimen of the drug; however, some aspects of the treatment of AD with SMO still remain controversial.. This is the first consensus study investigating the use of SMO for the treatment of AD through the opinions gained in over twenty years of clinical practice provided by fifty Italian expert clinicians. A consensus on good practice for the correct administration of SMO has clearly emerged; these opinions, along with those derived from previous clinical investigations, will help physicians to use SMO in a better way. However, some issues remain controversial, and others remain unresolved.

Topics: Alcoholism; Humans; Italy; Practice Guidelines as Topic; Sodium Oxybate; Surveys and Questionnaires

Topics: Alcoholism; Central Nervous System Depressants; Clinical Trials as Topic; Humans; Italy; Secondary Prevention; Sodium Oxybate; Substance Withdrawal Syndrome; Treatment Outcome

A number of compounds already in use as medications for various indications substitute for ethanol at clinically relevant brain pathways, in particular, at gamma-aminobutyric acid (GABA) receptors. Nevertheless, although substitute medications have been recognized for heroin and tobacco dependence, patients with alcohol dependence are rarely offered an analogous approach. Benzodiazepines may have paradoxical effects, and abuse and dependence are known. Baclofen (GABA(B) agonist) has not been associated with dependence or misuse and has been effective in several trials in preventing relapse, although research is required to establish the optimal dosing regimen. GABA-ergic anticonvulsants, helpful in treating withdrawal, have yet to emerge as effective in relapse prevention. Clomethiazole and sodium oxybate, the latter having been shown to be effective in relapse prevention, have incurred a reputation for dependence and abuse. However, data have emerged showing that the risk of abuse of sodium oxybate is lower than many clinicians had foreseen. For a condition where existing therapies are only effective in a proportion of patients, and which has high morbidity and mortality, the time now seems right for reappraising the use of substitute prescribing for alcohol dependence.

Topics: Alcoholism; Anticonvulsants; Benzodiazepines; Brain; Chlormethiazole; Drug-Related Side Effects and Adverse Reactions; GABA-B Receptor Agonists; Harm Reduction; Humans; Sodium Oxybate

Topics: Alcoholism; Hospitalization; Humans; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Sodium Oxybate; Substance Withdrawal Syndrome; Temperance; Treatment Outcome

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.. 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.. 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.

Topics: Adjuvants, Anesthesia; Adult; Alcoholism; Comorbidity; Drug Tolerance; Humans; Illicit Drugs; Male; Neuropsychological Tests; Sodium Oxybate; Substance Withdrawal Syndrome; Substance-Related Disorders; Treatment Outcome

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.

Topics: Adult; Alcoholism; Female; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Humans; Linear Models; Male; Reference Values; Sodium Oxybate

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).

Topics: Alcoholism; Baclofen; GABA Agonists; GABA-B Receptor Agonists; Humans; Sodium Oxybate

Topics: Alcohol Drinking; Alcoholism; Anesthetics, Intravenous; Drug Interactions; Humans; Illicit Drugs; Sodium Oxybate; Substance-Related Disorders

To describe the clinical features of gamma-hydroxybutyrate (GHB) and gamma-butyrolactone (GBL) toxicity.. Retrospective case-study of 65 GHB and GBL intoxications seen in an urban emergency department.. 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%).. 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.

Topics: 4-Butyrolactone; Adolescent; Adult; Alcoholism; Anesthetics, Intravenous; Bradycardia; Case-Control Studies; Coma; Drug Overdose; Female; Humans; Hypothermia; Male; Opioid-Related Disorders; Retrospective Studies; Sodium Oxybate; Solvents

Topics: Alcoholism; Animals; Humans; Sodium Oxybate

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.

Topics: Adjuvants, Anesthesia; Alcoholism; Humans; Male; Middle Aged; Self Medication; Sodium Oxybate; Substance Withdrawal Syndrome

Topics: Adolescent; Adult; Aged; Alcoholism; Ambulatory Care; Female; Follow-Up Studies; Humans; Male; Middle Aged; Sodium Oxybate; Treatment Outcome

Topics: Alcohol Deterrents; Alcoholism; Humans; Sodium Oxybate; Substance-Related Disorders

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.

Topics: Adolescent; Adult; Aged; Alcohol Withdrawal Delirium; Alcoholism; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neurologic Examination; Sodium Oxybate; Temperance

Topics: Alcoholism; Humans; Sodium Oxybate; Wernicke Encephalopathy

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.

Topics: 4-Butyrolactone; Alcoholism; Drug Monitoring; Ethanol; Gas Chromatography-Mass Spectrometry; Humans; Regression Analysis; Sensitivity and Specificity; Sodium Oxybate; Substance Withdrawal Syndrome

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.

Topics: Administration, Oral; Adult; Alcoholism; Humans; Male; Middle Aged; Sodium Oxybate

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.

Topics: Adult; Alcoholism; Blood Platelets; Catecholamines; Dopamine; Epinephrine; Humans; Hydroxybutyrates; Monoamine Oxidase; Norepinephrine; Serotonin; Sodium Oxybate

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.

Topics: Acetaldehyde; Alcoholism; Animals; Brain; Ethanol; Humans; Hydroxybutyrates; Liver; Male; Pyrazoles; Rats; Rats, Inbred Strains; Sodium Oxybate

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.

Topics: Adult; Alcoholism; Anti-Anxiety Agents; Benzodiazepines; Biureas; Ethanol; Humans; Male; Sodium Oxybate; Tranquilizing Agents

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.

Topics: Alcoholism; Animals; Anti-Anxiety Agents; Apomorphine; Benzodiazepines; Benzodiazepinones; Haloperidol; Humans; Male; Psychotropic Drugs; Rats; Sleep Wake Disorders; Sodium Oxybate; Substance Withdrawal Syndrome

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.

Topics: Adult; Alcoholism; Circadian Rhythm; Humans; Hydroxybutyrates; Male; Middle Aged; Sodium Oxybate