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

Frye, Mark A. MD; Hinton, David J. BA; Karpyak, Victor M. MD, PhD; Biernacka, Joanna M. PhD; Gunderson, Lee J. BS; Feeder, Scott E. MS; Choi, Doo-Sup PhD; Port, John D. MD, PhD

Journal of Clinical Psychopharmacology: December 2016 - Volume 36 - Issue 6 - p 669–674
doi: 10.1097/JCP.0000000000000590
Original Contributions

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these data would suggest a normalizing effect of acamprosate on a hyperglutamatergic state observed in recently withdrawn patients with alcohol dependence and a positive association between MACC glutamate levels and craving intensity in early abstinence.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.

From the Departments of *Psychiatry and Psychology and †Molecular Pharmacology and Experimental Therapeutics, ‡Neurobiology of Disease Program, §Health Sciences Research, and ∥Department of Radiology, Mayo Clinic College of Medicine, Rochester, MN.

Received April 11, 2016; accepted after revision August 24, 2016.

Reprints: Mark A. Frye, MD, Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905 (e-mail:

This study was funded by the Samuel Johnson Foundation for Genomics of Addiction Program at the Mayo Clinic (V.M.K. and D.S.C.) and by grants from the National Institutes of Health to M.A.F., V.M.K., D.A.M., and D.S.C. (P20 AA017830).

M.A.F. and D.J.H. contributed equally to this manuscript.

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