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Historically, most pharmacological approaches to the treatment of addictive disorders have utilized either substitution-based methods i. However, substantial evidence has accumulated indicating that ligands acting on glutamatergic transmission are also of potential utility in the treatment of drug addiction, as well as various behavioral addictions such as pathological gambling. The purpose of this review is to summarize the pharmacological mechanisms of action and general clinical efficacy of glutamatergic medications that are currently approved or are being investigated for approval for the treatment of addictive disorders. Medications with effects on glutamatergic transmission that will be discussed include acamprosate, N-acetylcysteine, D-cycloserine, gabapentin, lamotrigine, memantine, modafinil, and topiramate.

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