Anterior Cingulate Glutamate Is Reduced by Acamprosate Treatment in Patients with Alcohol Dependence

Mark A. Frye, David J. Hinton, Victor M. Karpyak, Joanna M. Biernacka, Lee J. Gunderson, Scott E. Feeder, Doo Sup Choi, John D. Port

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Although the precise drug mechanism of action of acamprosate remains unclear, its antidipsotropic effect is mediated in part through glutamatergic neurotransmission. We evaluated the effect of 4 weeks of acamprosate treatment in a cohort of 13 subjects with alcohol dependence (confirmed by a structured interview, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) on proton magnetic resonance spectroscopy glutamate levels in the midline anterior cingulate cortex (MACC). We compared levels of metabolites with a group of 16 healthy controls. The Pennsylvania Alcohol Craving Scale was used to assess craving intensity. At baseline, before treatment, the mean cerebrospinal fluid-corrected MACC glutamate (Glu) level was significantly elevated in subjects with alcohol dependence compared with controls (P = 0.004). Four weeks of acamprosate treatment reduced glutamate levels (P = 0.025), an effect that was not observed in subjects who did not take acamprosate. At baseline, there was a significant positive correlation between cravings, measured by the Pennsylvania Alcohol Craving Scale, and MACC (Glu) levels (P = 0.019). Overall, these data would suggest a normalizing effect of acamprosate on a hyperglutamatergic state observed in recently withdrawn patients with alcohol dependence and a positive association between MACC glutamate levels and craving intensity in early abstinence. Further research is needed to evaluate the use of these findings for clinical practice, including monitoring of craving intensity and individualized selection of treatment with antidipsotropic medications in subjects with alcohol dependence.

Original languageEnglish (US)
Pages (from-to)669-674
Number of pages6
JournalJournal of Clinical Psychopharmacology
Issue number6
StatePublished - Dec 1 2016


  • MACC
  • MRS
  • acamprosate
  • alcohol dependence
  • craving
  • glutamate

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)


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