Gamma Hydroxybutyric Acid (GHB) for the Treatment of Alcohol Dependence: A Review

Gamma-hydroxybutyric acid (GHB) is a short-chain fatty acid structurally similar to the inhibitory neurotransmitter γ-aminobutyric acid. Clinical trials have demonstrated that 50–100 mg/kg of GHB fractioned into three or six daily doses is able to suppress alcohol withdrawal symptoms and facilitates the maintenance of abstinence from alcohol. These studies have also shown that GHB craving episodes are a very limited phenomenon (about 10–15%). Thus, physicians with access should consider the clinical efficacy of GHB as a valid pharmacological tool for the treatment of alcohol addiction

A brief up-date of the use of sodium oxybate for the treatment of alcohol use disorder

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 -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

Alcohol use disorders in the elderly: A brief overview from epidemiology to treatment options

Alcohol-use-disorders (AUDs) afflict 1-3% of elderly subjects. The CAGE, SMAST-G, and AUDIT are the most common and validated questionnaires used to identify AUDs in the elderly, and some laboratory markers of alcohol abuse (AST, GGT, MCV, and CDT) may also be helpful. In particular, the sensitivity of MCV or GGT in detecting alcohol misuse is higher in older than in younger populations. The incidence of medical and neurological complications during alcohol withdrawal syndrome in elderly alcoholics is higher than in younger alcoholics. Chronic alcohol abuse is associated with tissue damage to several organs. Namely, an increased level of blood pressure is more frequent in the elderly than in younger adults, and a greater vulnerability to the onset of alcoholic liver disease, and an increasing risk of breast cancer in menopausal women have been described. In addition, the prevalence of dementia in elderly alcoholics is almost 5 times higher than in non-alcoholic elderly individuals, approximately 25% of elderly patients with dementia also present AUDs, and almost 20% of individuals aged 65 and over with a diagnosis of depression have a co-occurring AUD. Moreover, prevention of drinking relapse in older alcoholics is, in some cases, better than in younger patients; indeed, more than 20% of treated elderly alcohol-dependent patients remain abstinent after 4. years. Considering that the incidence of AUDs in the elderly is fairly high, and AUDs in the elderly are still underestimated, more studies in the fields of epidemiology, prevention and pharmacological and psychotherapeutic treatment of AUDs in the elderly are warranted. © 2012 Elsevier Inc

Gamma hydroxybutirric acid (GHB) withdrawal does not occur at therapeutic dosage

No abstract availabl

Alcohol use disorder and GABAB receptor gene polymorphisms in an Italian sample: haplotype frequencies, linkage disequilibrium and association studies

Background: Alcohol use disorder (AUD) is a complex trait with genetic and environmental influences. Several gene variants have been associated with the risk for AUD, including genes encoding the sub-units of the γ-aminobutyric acid (GABA) receptors. Aim: This study evaluated whether specific single nucleotide polymorphisms (SNPs) in genes encoding GABAB receptor sub-units can be considered as candidates for the risk of AUD. Subjects and methods: Seventy-four AUD subjects and 128 Italian controls were genotyped for 10 SNPs in genes encoding GABA-B1 and GABA-B2 sub-units (GABBR1 and GABBR2). Allele, genotype, and haplotype frequencies were tested for the association with the AUD trait. Results: A significant difference between AUD individuals and controls was observed at genotype level for rs2900512 of GABBR2 gene. The homozygous T/T genotype was not found in the controls, whereas it was over-represented in the AUD individuals. Under the recessive model (T/T vs C/T + C/C) this result was statistically significant, as well as the Odds Ratio for the association with the AUD trait. Conclusions: The results provide preliminary data on the association between GABAB receptor gene variation and risk of AUD. To confirm this finding, studies with larger samples and additional characterisation of the phenotypic AUD trait are required

Sodium oxybate in maintaining alcohol abstinence in alcoholic patients according to Lesch typologies: A pilot study

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. © The Author(s) 2013

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

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&nbsp;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. © 2007 Elsevier B.V. All rights reserved

Proposal for the enhancement of alcohology (prevention, treatment and rehabilitation of alcohol problems): the position of Società Italiana di Alcologia (SIA), Federazione Italiana degli Operatori dei Dipartimenti e dei Servizi delle Dipendenze (FeDerSerD) and Società Italiana Tossicodipendenze (SITD)

Proposal for the enhancement of alcohology (prevention, treatment and rehabilitation of alcohol problems): the position of Società Italiana di Alcologia (SIA), Federazione Italiana degli Operatori dei Dipartimenti e dei Servizi delle Dipendenze (FeDerSerD) and Società Italiana Tossicodipendenze (SITD