Gabapentin blocks calcium channels containing the alpha 2 delta 1 subunit and has other actions that may affect both glutamatergic and GABAergic neurotransmission, much the same as drinking alcohol does. It is FDA-approved for the treatment of neuralgia, partial seizures, and restless legs syndrome; however, recent studies are investigating gabapentin as a potential medication for mitigating withdrawal and preventing relapse in alcohol use disorder (AUD). In this study, the authors used proton MR spectroscopy (1H-MRS) to measure GABA and glutamate levels in the dorsal anterior cingulate (dACC) before and during gabapentin treatment for AUD. The 96 patients were randomized to 1200 mg/day of gabapentin (n=46) or placebo (n=50) after 72 or more hours of alcohol abstinence with imaging done prior to treatment and again 14 days later. Patients taking gabapentin were significantly more likely to remain abstinent over the 16-week study period compared to placebo (Figure). Imaging revealed that patients taking gabapentin who had remained abstinent on the majority of days had significantly greater increases (or smaller decreases) in glutamate between scans compared to placebo. Additionally, patients taking gabapentin had greater decreases (or smaller increases) in GABA between scans, dependent on days remained abstinent. Increases in glutamate levels between scans correlated with percent of days abstinent in patients taking gabapentin. Together, these data suggest that gabapentin may promote abstinence from alcohol by normalizing glutamatergic and GABAergic systems.

Reference:

Prisciandaro JJ et al. Am J Psychiatry 2021;00:1-9. Abtract