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

Caputo, Fabio; Addolorato, Giovanni; Stoppo, Michela; Francini, Sara; Vignoli, Teo; Lorenzini, Francesca; Re, Arfedele Del; Comaschi, Claudio; Andreone, Pietro; Trevisani, Franco; Bernardi, Mauro; Group, Alcohol Treatment Study

doi:10.1016/j.euroneuro.2007.04.008

Cited by 53 publications

(33 citation statements)

References 46 publications

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“…As ADE has been proposed and validated as an animal model of relapse episodes occurring in human alcoholics (see Spanagel, 2005; Martin-Fardon and Weiss, 2013), these data extend to relapse-like drinking the capacity of GHB to suppress different alcohol-related behaviors, including alcohol drinking under the two-bottle choice regimen (June et al, 1995; Agabio et al, 1998), operant oral alcohol self-administration (Maccioni et al, 2008), and alcohol-seeking behavior (Maccioni et al, 2008), in alcohol-preferring rats. These data are also in close agreement with the results of a number of clinical surveys reporting the capacity of GHB to promote and maintain alcohol abstinence and to prevent alcohol relapse (Gallimberti et al, 1992; Addolorato et al, 1996, 1998; Moncini et al, 2000; Maremmani et al, 2001; Caputo et al, 2003, 2007). …”

Section: Discussionsupporting

confidence: 88%

“…Several open and double-blind clinical surveys indicate indeed that GHB administration reduced alcohol craving and consumption, promoted abstinence, and ameliorated alcohol withdrawal syndrome in alcoholics. Specifically, a small double-blind study (Gallimberti et al, 1992) and some subsequent open studies (Addolorato et al, 1996, 1998; Moncini et al, 2000; Maremmani et al, 2001; Caputo et al, 2003, 2007, 2011) indicated that treatment with GHB was effective in reducing alcohol drinking, promoting abstinence, and controlling craving for alcohol (for review, see Agabio and Gessa, 2002; Addolorato et al, 2009). Further, three double-blind studies (Gallimberti et al, 1989; Addolorato et al, 1999a; Nimmerrichter et al, 2002) and some additional open studies (Nava et al, 2007; Elsing et al, 2009) reported that treatment with GHB was also effective in suppressing the symptomatology of alcohol withdrawal syndrome (for review, see Agabio and Gessa, 2002; Addolorato et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Suppression by γ-Hydroxybutyric Acid of “Alcohol Deprivation Effect” in Rats: Preclinical Evidence of its anti-Relapse Properties

2012

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γ-Hydroxybutyric acid (GHB) reduces (a) alcohol intake and alcohol motivational properties in alcohol-preferring rats and (b) alcohol drinking and craving for alcohol in human alcoholics. The present study was designed to extend to relapse-like drinking the capacity of GHB to suppress different alcohol-related behaviors in alcohol-preferring rats. The “alcohol deprivation effect,” defined as the temporary increase in alcohol intake occurring in laboratory animals after a period of alcohol deprivation, was used as model of alcohol relapse. Acute administration of non-sedative doses of GHB (0, 100, 200, and 300 mg/kg, i.p.) resulted in the complete suppression of the extra-amount of alcohol consumed by Sardinian alcohol-preferring rats during the first hour of re-access to alcohol after a 14-day period of deprivation. These data demonstrate that GHB suppressed relapse-like drinking in a rat model of excessive alcohol consumption.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Suppression by γ-Hydroxybutyric Acid of “Alcohol Deprivation Effect” in Rats: Preclinical Evidence of its anti-Relapse Properties

2012

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“…[8,9] Additionally, findings from the COMBINE (Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence) study, in which 1383 subjects were randomized to one of eight different treatment options including monotherapy with either oral naltrexone 100 mg/day or acamprosate 3 g/day, or combination therapy with these two medications, demonstrated that only naltrexone produced a statistically significant difference compared with placebo in increased percentage of days abstinent and decreased risk of heavy drinking. [10] Due to the lack of robust evidence in support of current FDA-approved treatments, a number of medications with novel mechanisms of action, including topiramate, [11][12][13][14] an NMDA receptor antagonist, and g-hydroxybutric acid [15][16][17] and baclofen, [18][19][20][21][22][23] both GABA B receptors agonists, have been studied. Of these treatments, baclofen has been one of the most studied to investigate its efficacy and safety for alcohol dependence.…”

Section: Introductionmentioning

confidence: 99%

Defining the Role of Baclofen for the Treatment of Alcohol Dependence

2012

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The pharmacological properties of baclofen, a GABA(B) receptor agonist, have led to investigation of its use for the off-label treatment of alcohol dependence. Literature examining the role of baclofen in alcohol dependence suggests that it may be a useful medication in the treatment armamentarium with an additional benefit of promoting abstinence and reducing alcohol-associated cravings and anxiety. We conducted a systematic review of prospective, randomized controlled trials comparing baclofen with placebo for the treatment of alcohol dependence. Four randomized controlled trials were identified but only three met criteria for inclusion. The excluded trial was a post hoc analysis of data collected from an original trial whose primary outcome did not fit our inclusion criteria and was terminated prior to completion. Compared with placebo, subjects randomized to baclofen experienced higher rates of abstinence and lower anxiety scores; the effect of baclofen was statistically significant in two trials assessing patients with more severe alcohol dependence and non-significant in a trial of outpatients receiving concomitant manualized psychotherapy. Baclofen appeared to be safe, well tolerated and to have low addiction liability even in the setting of moderate-to-severe liver cirrhosis, a known complication of alcohol dependence. Though baclofen may hold promise, the different outcomes and sample populations of the three studies highlight the need for more research to better understand the appropriate target patient population to benefit from this medication. Questions still remain about optimal dosing and duration. There is not enough evidence to support the use of baclofen as a first-line treatment option, except for those alcohol-dependent patients with moderate-to-severe liver cirrhosis in whom other pharmacological treatments are not safe or practical.

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“…This effect was not observed in the clinical studies with alcoholics reported above. In fact, no side effects due to the combination of GHB 50 mg/kg (divided into 3 to 6 daily administration) and alcohol were observed in those GHB-treated alcoholics who were still drinking during the treatment [39–41,44,45]. It is conceivable that the use of the same dose of 50 mg/kg divided into 3–6 daily administrations was able to prevent the occurrence of unsafe effects when associated with ethanol [46].…”

Section: Ghb As An Anti-craving Drug In the Maintenance Of Alcohol Abmentioning

confidence: 99%

“…In order to confirm this suggestion, a 3-month randomized study was performed in patients mostly with severe alcohol dependence [45]. In this 3-month open randomized comparative study, the combined treatment of GHB and NTX was shown to be more effective in maintaining abstinence from alcohol than GHB and NTX used singly, 72.2%, 40% and 5.9%, respectively [45]. The number of relapses into heavy drinking also tended to occur less frequently in the combination group (no cases) than in either the GHB group or the NTX group.…”

Section: Ghb As An Anti-craving Drug In the Maintenance Of Alcohol Abmentioning

confidence: 99%

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

Caputo

Vignoli

Maremmani

et al. 2009

IJERPH

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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.

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

Cited by 53 publications

References 46 publications

Suppression by γ-Hydroxybutyric Acid of “Alcohol Deprivation Effect” in Rats: Preclinical Evidence of its anti-Relapse Properties

Suppression by γ-Hydroxybutyric Acid of “Alcohol Deprivation Effect” in Rats: Preclinical Evidence of its anti-Relapse Properties

Defining the Role of Baclofen for the Treatment of Alcohol Dependence

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

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