Possible Interaction: Ethanol and Baclofen

“Finally, we review evidence of EAAT1/GLAST involvement … alcoholism and present some preliminary data showing that ethanol , at concentrations which may be reached following heavy drinking, can have … EAAT1/GLAST in cultured astrocytes; the effect is blocked by baclofen , a GABA-B receptor agonist … in the treatment of alcoholism.”

“Baclofen may be effective in reducing craving and alcohol drinking, although the facilitation of extinction and suppression of both alcohol and Tang self‐administration by baclofen suggests these effects may be related to a more general suppression of consummatory and conditioned behaviors.”

“Under within‐session extinction conditions, baclofen (1.8 and 2.4 mg/kg) facilitated extinction of responding for both alcohol and Tang, particularly during the first 10 minutes of extinction.”

“The majority of clinical surveys conducted to date have demonstrated the capacity of baclofen to suppress alcohol consumption, craving for alcohol , and alcohol withdrawal symptomatology in alcohol-dependent patients.”

“Acute treatment with baclofen also dose-dependently suppressed extinction responding for alcohol (an index of motivation to consume alcohol) in sP rats trained to lever-press for oral alcohol self-administration.”

“At a preclinical level, the repeated administration of non-sedative doses of baclofen dose-dependently suppressed the acquisition and maintenance of alcohol drinking behavior in selectively bred Sardinian alcohol-preferring (sP) rats tested under the homecage, 2-bottle “ alcohol vs water” choice regimen.”

“Further, acutely administered baclofen dose-dependently reduced the severity of alcohol withdrawal signs in Wistar rats made physically dependent upon alcohol.”

“Indeed, a doubleblind survey demonstrated that repeated daily treatment with baclofen was associated, when compared to placebo, with a higher percentage of subjects totally abstinent from alcohol and a higher number of days of total abstinence.”

“… baclofen … alcohol priming and self-administration, as indicated by significant interaction effects between drug condition (baclofen vs. placebo) and some of the priming variables (alcohol craving: … = 6.03, p = 0.01; alcohol sedation: F 3,6 = 7.16, p = 0.01) on the total amount of alcohol self-administered.”

“This property of baclofen makes it a promising agent in alcohol relapse prevention.”

“ Baclofen reduces the reinforcing effects of alcohol and other drugs in animals, providing justification for clinical studies in human beings.”

“Benzodiazepines, clomethiazole, tiagabine, vigabatrin, pregabalin, gabapentin, acamprosate, naltrexone, GHB, topiramate, ondansetron and baclofen at low dose (≤1 mg/kg, the dose range used in randomized trials in humans: 30 and 60 mg/day) have all been shown to at best reduce motivation to consume alcohol in rats.”

“Yet, after having both used my model, Bucknam titled his paper: ‘‘Suppression of symptoms of AD and craving using HD baclofen’’ while Agabio et al. titled their paper: ‘ Baclofen suppresses alcohol intake and craving for alcohol in a schizophrenic alcohol-dependent patient: a case report.’’”

“Moreover, the authors showed that ethanolexperienced mice were less sensitive … baclofen than naive mice, suggesting that the combination of baclofen … alcohol or baclofen alone would have less of a negative impact on alcoholic patients than … observation underlines further the safety of the drug in the treatment of alcohol addiction.”

“This observation could indicate that the possible crosstolerance between the sedative effect of ethanol and baclofen persists in alcoholic patients also after periods of abstinence.”