Biobehavioral effects of baclofen in anxious alcohol-dependent individuals: a randomized, double-blind, placebo-controlled, laboratory study

M Farokhnia, M L Schwandt, M R Lee, J W Bollinger, L A Farinelli, J P Amodio, L Sewell, T A Lionetti, D E Spero, L Leggio, M Farokhnia, M L Schwandt, M R Lee, J W Bollinger, L A Farinelli, J P Amodio, L Sewell, T A Lionetti, D E Spero, L Leggio

Abstract

Baclofen has been suggested as a potential pharmacotherapy for alcohol use disorder, but the clinical data are conflicting. Here we investigated the biobehavioral effects of baclofen in a sample of anxious alcohol-dependent individuals. This was a randomized, double-blind, placebo-controlled, human laboratory study in non-treatment seeking alcohol-dependent individuals with high trait anxiety (N=34). Participants received baclofen (30 mg per day) or placebo for at least 8 days, then performed an experimental session consisting of alcohol cue-reactivity followed by alcohol administration procedure (alcohol priming, then alcohol self-administration). Total amount of alcohol self-administered was the primary outcome; alcohol craving, subjective/physiological responses and mood/anxiety symptoms were also evaluated. There was no significant medication effect on the total amount of alcohol consumed during the alcohol self-administration (P=0.76). Baclofen blunted the positive association between maximum breath alcohol concentration during priming and the amount of alcohol consumption (significant interaction, P=0.03). Ratings of feeling intoxicated were significantly higher in the baclofen group after consuming the priming drink (P=0.006). During the self-administration session, baclofen significantly increased ratings of feeling high (P=0.01) and intoxicated (P=0.01). A significant reduction in heart rate (P<0.001) and a trend-level increase in diastolic blood pressure (P=0.06) were also detected in the baclofen group during the alcohol laboratory session. In conclusion, baclofen was shown to affect subjective and physiological responses to alcohol drinking in anxious alcohol-dependent individuals. These results do not support an anti-craving or anti-reinforcing effect of baclofen, but rather suggest that baclofen may act as a substitution medication for alcohol use disorder.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic outline of the study flow. AAS, Alcohol Attention Scale; AUQ, Alcohol Urge Questionnaire; BAES, Biphasic Alcohol Effects Scale; BMI, body mass index; BrAC, breath alcohol concentration; BSA, Brief Scale for Anxiety; CIWA-Ar, Clinical Institute Withdrawal Assessment for Alcohol-revised; C-SSRS, Columbia Suicide Severity Rating Scale; DEQ, Drug Effects Questionnaire; MADRS, Montgomery–Åsberg Depression Rating Scale; OCDS, Obsessive Compulsive Drinking Scale; POMS, Profile of Mood States; STAI, Spielberger State Trait Anxiety Inventory; t.i.d., three times a day; TLFB, Timeline Followback.
Figure 2
Figure 2
Flow diagram of the study. BrAC, breath alcohol concentration.
Figure 3
Figure 3
(a) Total amount of alcohol consumed during alcohol self-administration; (b) medication × max-BrAC interaction effect on the total amount of alcohol consumed during alcohol self-administration. Note: statistical analysis showed no outliers; the results remained significant after excluding the two subjects with high BrAC (far right); (c) breath alcohol concentrations during the priming (left) and ASA (right) phases. AP, alcohol priming; ASA, alcohol self-administration; BAC, baclofen; BrAC, breath alcohol concentration; M, mean; Max, maximum; PLC, placebo; SEM, standard error of the mean.
Figure 4
Figure 4
DEQ ratings during the alcohol priming (left) and ASA (right): (a) ‘Do you feel intoxicated?' (significant medication effect); (b) ‘Do you feel high?' (significant medication effect); (c) ‘Do you like the effects you are feeling now?' (significant time × medication interaction effect, #P=0.09 (post-hoc analysis)); (d) ‘Do you feel any drug effects?' (e) ‘Would you like more of what you received, right now?' *P<0.05, **P<0.01. AP, alcohol priming; ASA, alcohol self-administration; BAC, baclofen; BrAC, breath alcohol concentration; DEQ, Drug Effects Questionnaire; M, mean; PLC, placebo; SEM, standard error of the mean.

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