Increased sensitivity to sedatives manifested by the inebriate—a phenomenon well known to those who "spike" their drinks—is generally attributed to additive effects of alcohol and sedative drugs on the central nervous system. On the other hand, the seemingly paradoxical decreased sensitivity to sedatives as well as to alcohol observed in chronic alcoholics is usually ascribed to adaptation by the central nervous system to drug habituation. Both explanations have to be reexamined in the light of recent studies at the cellular and subcellular levels. Emphasis appears to be shifting from the brain to the liver.
Studies on the metabolism of pentobarbital and meprobamate in acutely inebriated rats and human volunteers by Rubin and associates1 showed that there was a significant slowing in the disappearance of these drugs from the blood of both the men and the rats. That the slowing was due to a direct effect of alcohol on hepatic
Alcohol-Induced Sensitivity and Tolerance. JAMA. 1972;219(4):508-509. doi:10.1001/jama.1972.03190300044015