• Energy Research

Background: Ghrelin is a peptide produced mainly by the gut and hypothalamus. Ghrelin is able to stimulate food‐seeking behavior. Alcohol‐craving and food‐seeking behavior could share common neural circuits. Ghrelin is related to nutritional status, but few data are available in alcoholic patients on the relationship between ghrelin and nutritional disorders.Methods: Plasma ghrelin was evaluated in 15 current alcoholic male patients compared with 15 healthy male volunteers. Craving was evaluated by the Obsessive–Compulsive Drinking Scale. Body composition was assessed by dual‐energy X‐ray absorptiometry. Energy substrate utilization was evaluated by indirect calorimetry.Results: Ghrelin was significantly reduced in alcohol‐dependent patients with respect to healthy subjects (p=0.0278). A significant positive correlation was found between ghrelin and craving (r=0.55; p=0.034). A preferential utilization of lipids as an energy substrate with a reduction of the fat mass (p=0.01) and an increase of the free fat mass (p=0.0091) was found in alcoholic patients.Conclusions: Within our sample showing low ghrelin levels probably related to the impaired nutritional status; patients with higher levels of ghrelin showed higher levels of alcohol craving. These preliminary data indicate that ghrelin could be implicated in the neurobiological mechanisms of alcohol craving, other than a hormone influenced by the nutritional status.

To explore the effect of baclofen in a dose of 20 mg three times per day, compared with the already studied dose of 10 mg three times per day, in the treatment of alcohol dependence.We present a secondary analysis of a 12-week double-blind, placebo-controlled, randomized clinical trial with two doses of baclofen, specifically 10 mg t.i.d. and 20 mg t.i.d. Out of 94 subjects consecutively screened, 42 were randomized into the study. Fourteen of the 42 patients were randomly allocated to placebo, 14 to the group treated with baclofen 10 mg t.i.d. (B10 mg) and 14 to the group treated with baclofen 20 mg t.i.d. (B20 mg).Compared with patients allocated to placebo, patients allocated to the B10 mg group had a 53% reduction in the number of drinks per day (P < 0.0001) and patients allocated to the B20 mg group had a 68% reduction in the number of drinks per day (P < 0.0001), with respect to the number of drinks per day during the 28 days before randomization. The effect of baclofen 20 mg t.i.d. was greater than that of baclofen 10 mg t.i.d. (P = 0.0214, Wald test) showing a dose-effect relationship. Both doses of baclofen were well tolerated.This is provisional evidence of a dose-response effect for baclofen in the treatment of alcohol dependence.

Background: 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. Aims: To confirm the SMO effect on (sustained) MoA in detoxified alcohol-dependent patients. Methods: 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. Results: 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; p = 0.001). Since significant heterogeneity of effect across sites and unequal sample sizes among sites ( n = 3–66) were identified, a site-level random meta-analysis was performed with results supporting the pre-specified analysis: mean difference +32.4 days, p = 0.014. The SMO effect was sustained during the medication-free follow-up period. SMO was well-tolerated. Conclusions: Results of this large RCT in alcohol-dependent patients demonstrated a significant and clinically relevant sustained effect of SMO on CAD. Trial registration: ClinicalTrials.gov Identifier: NCT04648423

Acute alcohol intoxication is a clinically harmful condition that usually follows the ingestion of a large amount of alcohol. Clinical manifestations are heterogeneous and involve different organs and apparatuses, with behavioral, cardiac, gastrointestinal, pulmonary, neurological, and metabolic effects. The management of an intoxicated patient occurs mainly in the emergency department and is aimed at stabilizing the clinical condition of the patient, depending on his/her clinical presentation. One specific drug that is useful in the treatment of acute alcohol intoxication is metadoxine, which is able to accelerate ethanol excretion. In patients presenting an acute alcohol intoxication, alcohol-related disorders should be detected so that the patient can be directed to an alcohol treatment unit, where a personalized, specific treatment can be established.