• Energy Research

Four in-patients with moderate alcohol-withdrawal syndromes benefited from treatment with gabapentin administered in an add-on fashion to clomethiazole. In comparison with the amount of clomethiazole required as estimated using a specially developed score during previous detoxifications of these patients at our hospital, gabapentin (400 mg q.i.d.) clearly reduced the amount of clomethiazole needed now Gabapentin, an anticonvulsant with favorable pharmacokinetic properties and tolerability, and with no known risk of dependence, may therefore be a useful new drug in the treatment of alcohol withdrawal. We believe that the potential value of gabapentin in alcohol withdrawal deserves further controlled studies.

Objective: Alcohol withdrawal syndrome (AWS) is a serious complication of alcohol dependence and often requires intensive medical treatment. Antiepileptic drugs (AEDs) have been shown to be as efficacious in the treatment of AWS in several controlled trials as benzodiazepines and superior to placebo in relieving alcohol withdrawal symptoms. Oxcarbazepine (OXC), a newer anticonvulsive drug, has a favorable safety profile over carbamazepine (CBZ) and other older AEDs due to its excellent efficacy and better side‐effect profile.Methods: The efficacy and tolerability of OXC versus placebo were investigated in 50 inpatients during a 6‐day treatment of alcohol withdrawal in a 4‐site, double‐blind, randomized, placebo‐controlled pilot study. The amount of rescue medication of clomethiazole (CLO) capsules needed was chosen as the primary variable. The data were collected between May 2003 and September 2004.Results: No initial differences were found regarding sociodemographic data and alcohol‐related parameters, indicating successful randomization. No differences were found in the need for rescue medication CLO, decrease of withdrawal symptoms, or craving for alcohol between the OXC and the placebo group. Subjectively experienced side effects, normalization of vegetative parameters, craving, or improvement of psychopathological parameters were not different between the groups.Conclusion: Despite the negative finding, which may be attributable to the design of the study, OXC still poses an interesting alternative to CBZ and other drugs because other studies have found it not only as efficient but also as having no addictive potential, while additionally possessing an anti‐craving effect. Therefore, well‐designed investigations with larger cohorts are required to further elucidate this issue.

Binocular depth inversion represents an illusion of visual perception. Such inversion does not occur in all cases, especially when objects with a higher degree of familiarity (e.g. photographs of faces) are displayed. Cognitive factors are assumed to override the binocular disparity cues of stereopsis. We tested the hypothesis that during alcohol withdrawal the human CNS is unable to correct the implausible perceptual hypothesis. Measurements of binocular depth inversion in perception of 3D objects were performed in 10 patients with mild alcohol withdrawal and in 11 healthy volunteers. The binocular depth inversion scores were highly elevated in the patients group in comparison to the healthy volunteers. The data demonstrates a strong impairment of binocular depth inversion in alcohol withdrawal and support the view that alcohol withdrawal may be accompanied by a disorganization of the interaction between sensory input and generation of perceptual hypotheses.

Recent evidence suggests an involvement of the endocannabinoid system in the regulation of emotional behaviour and ethanol intake. Here we investigated age-specific acute behavioural effects of the cannabinoid receptor agonist WIN 55,212-2 (WIN) on anxiety-related behaviour and voluntary ethanol consumption in rats. Animals were treated with WIN (1.2 mg/kg)/vehicle at puberty onset on postnatal day (PD) 40, or at adulthood (PD 100). Animals were tested in the elevated plus-maze (EPM) and the light/dark emergence test (EMT) and for the initial response to alcohol in a free-choice ethanol consumption paradigm. Acute WIN treatment increased anxiety-related behaviours, and this effect was found to be partially more pronounced in pubertal than adult rats. Additionally, increased intake of higher ethanol solutions after cannabinoid treatment was only observed in pubertal rats. These drug-induced behavioural changes during puberty are paralleled by induction of the NR1 subunit of the NMDA receptor in the medial prefrontal cortex and the striatum. Moreover, pubertal but not adult WIN administration increased the levels of the scaffold protein Homer in these brain regions. Enhanced CB₁ receptor levels in the reinforcement system were also observed in pubertal compared to adult rats. These data support the notion that puberty is a highly vulnerable period for the aversive effects of cannabinoid exposure. In particular, augmented ethanol intake in pubertal cannabinoid-exposed animals might be related to some extent to increased emotional behaviour and in particular to enhanced NMDA and CB₁ receptor signalling.