ABSTRACT This paper reviews the current status of the adrenochrome theory of schizophrenia. An account is first given of all the experiments in which adrenochrome was reported to induce psychotomimetic effects in normal volunteers. Then the evidence is presented that adrenochrome may actually occur in the brain as a metabolite of adrenaline in the C2 group of adrenergic neurons in the medulla, together with an account of current ideas of the function of these neurons in higher limbic functions. Lastly the recent evidence is reviewed that the gene for the enzyme glutathione S-transferase is defective in schizophrenia. This enzyme detoxifies adrenochrome.
Working in a psychiatrically innovative environment created by the Government of Saskatchewan, Canada, Abram Hoffer and Humphry F. Osmond enunciated the adrenochrome hypothesis for the biogenesis of schizophrenia in 1952, slightly later proposing and, apparently, demonstrating, in a double-blind study, that the symptoms of the illness could be reversed by administering large doses of niacin. After placing the hypothesis within its ideological framework, the author describes its emergence and elaboration and discusses the empirical evidence brought against it. Hoffer's idiosyncratic diagnostic procedures, especially his creation and use of a supposed biochemical marker for schizophrenia, are examined. The author argues that Hoffer's conceptualization of schizophrenia, as well as his treatment approach, depended on a tautology. Following David Healy, the author treats the adrenochrome hypothesis as a version of a transmethylation theory, thus incorporating it into mainstream psychopharmacology.
The adrenochrome hypothesis of schizophrenia revisited https://pubmed.ncbi.nlm.nih.gov/12829415/
Hallucinogens as hard science: the adrenochrome hypothesis for the biogenesis of schizophrenia https://pubmed.ncbi.nlm.nih.gov/20533770/
THE ADRENOCHROME THEORY OF SCHIZOPHRENIA: A REVIEW https://pubmed.ncbi.nlm.nih.gov/14130059/