Neurometabolite Levels in Alcohol Use Disorder Patients During Baclofen Treatment and Prediction of Relapse to Heavy Drinking.

Baclofen, a GABA agonist, is used as a treatment for alcohol dependence. We aimed to examine brain metabolites following administration of baclofen or placebo in alcohol dependent individuals enrolled in a randomized placebo-controlled trial. Participants included 31 alcohol dependent individuals (recent drinking: = 16; and abstinent: = 15) who had received daily baclofen (BAC 30-75 mg = 20) or placebo (PL = 11) for at least 2 weeks (average 17 days). Using proton magnetic resonance spectroscopy (H-MRS), spectra from the right parietal lobe were analyzed to obtain measures of GABA, Glutamate (Glu), Glutathione (GSH) and N-Acetyl Apartate (NAA) 120 min following administration of PL or BAC. When weighting alcohol dependent participants according to recent alcohol consumption (within 24 h), there were significant differences between BAC and PL on parietal concentrations of GSH ( < 0.01) and NAA ( < 0.05). Multiple linear regression revealed a significant predictive effect of GSH on heavy drinking days at 12 weeks follow-up (Model: = 14.28, = 0.85; GSH: = -1.22, = 0.01) and also percentage days abstinent at 12 weeks follow-up (Model: = 6.50, = 0.72; GSH: = 0.99, = 0.06). Our data provide preliminary evidence that the effect of baclofen may be mediated by increased parietal concentrations of the antioxidant GSH and NAA in recently drinking alcohol dependent patients. GSH/Cr levels were also predictive of improved drinking outcomes in the trial and suggests a role for neural oxidative stress in alcohol use disorder.