Alcohol Withdrawal and Limbic Kindling:A Hypothesis of Relapse

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Abstract
In this concept paper, the authors review the arguments and evidence for the hypothesized link between the alcohol withdrawal syndrome and the anxiety and craving that occurs during abstinence in alcohol‐dependent patients. This hypothetical construct suggests that the repeated experience of alcohol withdrawal and its associated limbic‐neuronal discharge induces a permanent state of limbic hyperexcitability. This phenomenon has been referred to as “kindling.” Subsequent episodes of limbic discharge may then be precipitated during abstinence by alcohol‐related cues or may even occur spontaneously. Subjectively experienced as anxiety or craving, such a neuronal discharge could provoke relapse to drinking in vulnerable subjects. The clinical, neurochemical, and electrophysiologic rationale for this hypothesis will be presented, along with implications for treatment and suggested future studies.