It is established that 30-50% of alcoholics relapse during the first three months after stopping drinking. Why this period is particularly vulnerable for relapse is not clear. Clinical research has confirmed impaired sleep, mood instability, and anxiety, indicators of brain hyperexcitability, during the early abstinence period. These early abstinence, or protracted withdrawal, symptoms, although not yet well characterized or quantified, are reported to be poorly tolerated by the client and are suggested to play a role in craving and relapse to alcohol use. Targeting these symptoms with a medication that does not, itself, have abuse potential is hypothesized to result in improved treatment outcome. The medication chosen to target these early abstinence symptoms is the anticonvulsant gabapentin. The proposal takes advantage of a unique program at our affiliated Veterans Administration Medical Center (VAMC) that provides residential housing and intensive substance abuse treatment for 4 weeks, as long as a client is verified as alcohol-free. This setting is ideal, since the dependent variables of interest (sleep, mood, brain activity) will not be influenced by the presence of alcohol. The hypothesis being tested is that the gabapentin-treated group, as compared to the placebo-treated group, will show improvements in behavioral (i.e., sleep, anxiety, mood) and neurological (i.e., acoustic startle and transcranial magnetic stimulation) indices. In addition, the study will explore if treatment with gabapentin during this 4-week early abstinence period decreases relapse to drinking in the month following discontinuation of pharmacotherapy and discharge from the intensive outpatient residential treatment program and will explore if gabapentin is equally effective in medically detoxified alcoholics as in non-medically detoxified alcoholics. This proposal builds on our previous experience with pharmacotherapy and behavioral/neurological characterization of acute alcohol detoxification. It extends our investigations to the early abstinence period and to a clinical treatment setting, specifically targeting protracted withdrawal symptoms with the anticonvulsant gabapentin. By using behavior, acoustic startle reflex and transcranial magnetic stimulation technologies, the study will also allow a systematic investigation of the relationship between persistent brain abnormalities and self-reported craving. This information has important implications for relapse prevention.

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National Institute on Alcohol Abuse and Alcoholism (NIAAA)
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Medical University of South Carolina
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Haun, Harold L; Griffin, William C; Lopez, Marcelo F et al. (2018) Increasing Brain-Derived Neurotrophic Factor (BDNF) in medial prefrontal cortex selectively reduces excessive drinking in ethanol dependent mice. Neuropharmacology 140:35-42
Schacht, Joseph P; Voronin, Konstantin E; Randall, Patrick K et al. (2018) Dopaminergic Genetic Variation Influences Aripiprazole Effects on Alcohol Self-Administration and the Neural Response to Alcohol Cues in a Randomized Trial. Neuropsychopharmacology 43:1247-1256
McGuier, Natalie S; Rinker, Jennifer A; Cannady, Reginald et al. (2018) Identification and validation of midbrain Kcnq4 regulation of heavy alcohol consumption in rodents. Neuropharmacology 138:10-19
Nimitvilai, Sudarat; Lopez, Marcelo F; Woodward, John J (2018) Effects of monoamines on the intrinsic excitability of lateral orbitofrontal cortex neurons in alcohol-dependent and non-dependent female mice. Neuropharmacology 137:1-12
Dowdle, Logan T; Brown, Truman R; George, Mark S et al. (2018) Single pulse TMS to the DLPFC, compared to a matched sham control, induces a direct, causal increase in caudate, cingulate, and thalamic BOLD signal. Brain Stimul 11:789-796
Zamudio-Bulcock, Paula A; Homanics, Gregg E; Woodward, John J (2018) Loss of Ethanol Inhibition of N-Methyl-D-Aspartate Receptor-Mediated Currents and Plasticity of Cerebellar Synapses in Mice Expressing the GluN1(F639A) Subunit. Alcohol Clin Exp Res 42:698-705
Cannady, Reginald; Rinker, Jennifer A; Nimitvilai, Sudarat et al. (2018) Chronic Alcohol, Intrinsic Excitability, and Potassium Channels: Neuroadaptations and Drinking Behavior. Handb Exp Pharmacol 248:311
Harlan, Benjamin A; Becker, Howard C; Woodward, John J et al. (2018) Opposing actions of CRF-R1 and CB1 receptors on VTA-GABAergic plasticity following chronic exposure to ethanol. Neuropsychopharmacology 43:2064-2074
Hanlon, Colleen A; Dowdle, Logan T; Henderson, J Scott (2018) Modulating Neural Circuits with Transcranial Magnetic Stimulation: Implications for Addiction Treatment Development. Pharmacol Rev 70:661-683
Hanlon, Colleen A; Dowdle, Logan T; Gibson, Nicole B et al. (2018) Cortical substrates of cue-reactivity in multiple substance dependent populations: transdiagnostic relevance of the medial prefrontal cortex. Transl Psychiatry 8:186

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