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Med Hypotheses. 1981 Feb;7(2):231-49.

Pathophysiology of the alcohol withdrawal syndrome.


A characteristic withdrawal syndrome appears following the interruption of chronic heavy consumption of alcoholic beverages. The pathophysiological elaborations of the various withdrawal signs and symptoms are considered. Among the unlikely, although plausible, pathophysiologic mechanisms of the tremulousness and skeletal muscle hyperreactivity of withdrawal is the accumulation or the sustained production of one or more circulating "toxic substances." Evidence consistent with such a mechanism includes the reported alleviation by dialysis of an impending withdrawal syndrome in alcoholic patients, the appearance of reflex hyperreactivity in withdrawing animals below the level of a chronic section of the spinal cord, and the time course of the appearance and disappearance of withdrawal syndromes. The various potential pathophysiological and neurochemical manifestations of the withdrawal illness are discussed--alterations in neural inhibition, in alpha-aminobutyric acid, catecholamines, acetylcholine, dopamine, prostaglandin, and in peptides. Experimental tests whereby a "toxic substance hypothesis" of withdrawal can be ruled in or out are proposed.

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