Many features of manic-depressive illness can be mimicked in man by the use and withdrawal of amphetamines. In higher doses these drugs induce a syndrome virtually indistinguishable from paranoid schizophrenia. In this paper, some of the biochemical and physiological effects of the amphetamines are examined with the hope of clarifying the nature of the biological changes in these two major functional psychoses. The actions of the amphetamines are shown to reveal the operation of specific homeostatic or adaptive nervous mechanisms. These appear likely also to operate in adaptation to psychological stress. Evidence is presented that these mechanisms are malfunctioning in manic-depressive and acute schizophrenic states and that this accounts for many of the clinical features of these conditions.

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