validation of a test system for development of medications for alcoholism

Conditions: Alcoholism

Summary: using thetema (test system for development of medications for alcoholism) it can be shown, that naltrexone administration reduces the willingness to perform work for alcohol infusion in a laboratory experiment.

objective of this study is to show that a laboratory alcohol self-administration method can predict the therapeutic potential of new compounds to reduce relapse in alcohol-dependent patients. the 'tema" translates several animal behavioral paradigms of alcohol self-administration into corresponding human experiments. we will investigate the opiate antagonist naltrexone, whose anti-relapse effect is well documented, as a reference drug for validation. main objective: with tema (test system for development of medications for alcoholism ) it can be shown, that naltrexone administration reduces the willingness to perform work for alcohol infusion in a laboratory experiment. secondary objectives: * administration of naltrexone in comparison to placebo leads to a reduction of alcohol craving and real-life drinking * administration of naltrexone in comparison to placebo leads to reduction of the cdt-level * administration of naltrexone in comparison to placebo leads to a change in perception of subjective alcohol effects * the effectiveness of naltrexone can be predicted by the a118g polymorphism of the oprm1 * administration of naltrexone changes the baseline and alcohol-induced ability of motor inhibition * administration of naltrexone changes the baseline and alcohol-induced regional cerebral perfusion * administration of naltrexone changes the baseline and alcohol-induced cerebral resting state activity * changes of alcohol effects to the brain activity induced by naltrexone in comparison to placebo correlate with effects of naltrexone on the willingness to work for alcohol self-administration

Eligibility criteria:
inclusion criteria: * male and female volunteers aged 25 to 55 years * at least weekly alcohol consumption at a medium risk level according to who in the timeline follow-back interview over the last 45 day with an average amount of alcohol of 41 g/day (men) or 31 g/day (women) * at least 6 days with an alcohol consumption of \>100 g/day (men) or 75 g/day (women) and at least 4 non consecutive alcohol abstinent days in the last 45 days * at least 1 drinking day in each full week between screening and visit 1 and not more than 6 abstinent days in the week before visit 1 * no demand of treatment of the risky alcohol consumption * written consent after information exclusion criteria: * a history of hypersensitivity against alcohol or one of the used medicinal products, of their ingredients or medicinal products with similar chemical structures * participation in another clinical trial within the last 4 weeks before inclusion * addiction or other disorders, which will not allow the subject to assess the character and importance or possible consequences of the clinical trial * pregnant or breastfeeding women * women capable of bearing children, except women who fulfil following criteria:- post-menopausal (12 months natural amenorrhoea or 6 month amenorrhoea and serum fsh \>40 ml u/ml) - post operative (6 weeks after ovariectomy on both sides with or without hysterectomy) - regular and correct use of a contraceptive method with an error quote of \< 1 % per year (for example implants, depot injections, oral contraceptive, iup). it has to be recognized that a combined oral contraception - in contrast to pure progesterone compounds - have a failure rate of \< 1 %. hormone iuds with a pearl index of 1 % are safer than copper iuds. - sexual abstinence - vasectomy of the partner * evidence that the participant is not expected to comply with the protocol (for example lacking compliance) * current or previous alcohol or substance dependence according to dsm-iv (exception: tobacco dependence) * current or previous treatment because of alcohol, for example in an addiction advisory cen-tre, self-help group, detoxification treatment * current or previous diseases, where an alcohol infusion can cause a clinically relevant hazard (e. g. pancreatitis, liver cirrhosis) * current or planned intake of opiate analgesics * current psychiatric treatment or intake of psychiatric drug or suffering from of a psychiatric disease requiring treatment * a history of suicide attempt * ciwa-score \>5 at screening (alcohol withdrawal scale) * a history of symptoms of alcohol withdrawal, epileptic seizures or delirium * routine laboratory parameters, indicating relevant liver-, pancreas- or kidney injury, an acute infection, anaemia or lack of vitamins (asat, alat \> twofold of the standard at screening, gamma-gt, lipase \>threefold of the standard, crp \ 12000/µl, haemoglobin \ 100 fl) * body weight \> 130 kg * drug screening in urine: once positive at screening for opiate, cannabis, cocaine, amphetamines, benzodiazepines or positive once at visit 1 for opiates or positive twice at visit 1 for cannabis, cocaine, amphetamines, benzodiazepines * breath alcohol concentration at screening once \> 0,00 g/kg or twice \>0,00 g/kg at visit 1 * unsuitable for fmrt (e. g. cardiac pacemaker, claustrophobia) * specific contraindications against naltrexone: o acute hepatitis o severe or acute liver disease o severe kidney disease o rare hereditary galactose intolerance, lapp-lactase-deficiency or glucose-galactose-malabsorption

Keywords: alcoholism alcohol self-administration