The Adrenochrome Hypothesis and Psychiatry

The adrenochrome hypothesis of schizophrenia (Hoffer, Osmond and Smythies, 1954), was stimulated by the work of Osmond and Smythies (1952) which focused on methylated derivatives of adrenalin as possible endogenous schizophrenogens. They showed that the experience which followed the ingestion of mescaline was in many ways similar to the experience induced in normal people by schizophrenia. This drew attention to derivatives of adrenalin (and of all the sympathomimetic amines and their precursors) as etiological factors. However, in 1952 very few of these compounds had been studied. With our resources we were forced to limit our studies to one derivative, adrenochrome, an oxidized, coloured derivative of adrenalin. So little was known about its chemistry it was not surprising chemists had concluded, incorrectly, it was inherently unstable and difficult to study. We allocated much of our chemical researches to this interesting substance. As a result, under the direction of Dr. R. Heacock (1959, 1965), an enormous body of data was gathered and published detailing the chemistry of adrenochrome, its synthesis, metabolism, conversion to other products and its reactions with substances like ascorbic acid. Adrenochrome is a member of a class of chemicals known as aminochromes, each one derived by the oxidation of its precursor amine. Thus, 1-dihydroxy phenylalanine (1-dopa) is oxidized to dopachrome; tyrosine to a series of coloured indoles; noradrenalin to noradrenochrome and adrenalin to adrenochrome. The chemistry of these oxidation reactions is very complex for these compounds are very reactive. They are formed via free radicals and rapidly break down to several classes of trihydroxy and dihydroxy N methyl indoles. Adrenolutin is the best known example of trihydroxy N methyl indole, and leukoadrenochrome is the best known