Acute interaction of baclofen in combination with alcohol in heavy social drinkers

Abstract

Background: There is growing evidence that gamma-amino butyric acid-B receptor agonists may be effective in the treatment of alcohol abuse or dependence. The primary goal of this study was to determine the safety of baclofen in combination with alcohol consumption in heavy drinkers. In addition, the effects of baclofen alone, and in combination with alcohol, on subjective effects, cognitive performance effects, as well as alcohol craving, were assessed.

Methods: Eighteen non-treatment-seeking heavy social drinkers (mean of 28 drinks per week), who did not meet the criteria for alcohol dependence participated. All individuals were tested using a double-blind double-dummy design with six 2-day inpatient phases. Baclofen (0, 40, and 80 mg) was administered 2.5 hours before alcohol (1.5 g/l body water or approximately 0.75 g/kg) or placebo beverages, given in 4 divided doses every 20 minutes.

Results: Baclofen, either alone or in combination with alcohol, produced only modest increases in heart rate and blood pressure and no adverse effects were reported. Baclofen did not increase positive subjective effects (e.g., Stimulant effects, Drug Liking) but did increase sedation and impair performance. Even though both baclofen and alcohol impaired performance, for the most part performance was not impaired to a greater extent when baclofen was combined with alcohol. Among this population of nondependent drinkers, baclofen did not alter alcohol craving or alcohol-induced positive subjective effects.

Conclusions: Baclofen alone has minimal abuse liability in heavy social drinkers, and baclofen is relatively well tolerated and safe when given in combination with intoxicating doses of alcohol.

Figures

Fig. 1

Mean breath alcohol concentrations as a function of baclofen dose and time after drinking four alcoholic beverages (approximately 0.75 g/kg body weight). Only active doses of alcohol are shown since all measurements for placebo beverages were 0. Data points show means of 18 individuals; vertical bars show ± 1 S.E.M. Some error bars have been omitted for clarity and the absence of any bars indicates 1 S.E.M. fell within the area of the data symbol. ALC Bev = alcohol beverage; min = minutes.

Fig. 2

Mean heart rate after baclofen alone (left panel) or baclofen in combination with alcohol (right panel) as a function of baclofen dose and time. PBO Bev = Placebo beverage; ALC Bev = alcohol beverage; Alc = alcohol; bpm = beats per minute; min = minutes. See Figure 1 for details.

Fig. 3

Mean BAES (Biphasic Alcohol Effects Scale) Summary Scores (range 0–70) and Alcohol Craving Scores (range 7–70) after baclofen alone (left panels) or baclofen in combination with alcohol (right panels) as a function of baclofen dose and time. * indicates a significant difference from 0 mg baclofen and 80 mg baclofen for a given time point, ** indicates a significant difference from 0 mg baclofen and 40 mg baclofen for a given time point. See Figure 1 and 2 for details.

Fig. 4

Mean ratings of Good Drug Effects and Drug Strength after baclofen alone (left panels) or baclofen in combination with alcohol (right panels) as a function of baclofen dose and time. Ratings for Good Drug Effects and Drug Strength could range from 0–4. See Figures 1–3 for details.

Fig. 5

Mean scores on selected performance measures after baclofen alone (left panels) or baclofen in combination with alcohol (right panels) as a function of baclofen dose and time. DAT = Divided Attention Task; DSST = Digit Symbol Substitution Task. See Figures 1–3 for details.