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HOFFER A, OSMOND H, SMYTHIES J. 
“Schizophrenia; a new approachIIResult of a year's research”. 
J Ment Sci. 1954 Jan 01;100(418):29-45.
Abstract
ABOUT one year ago, with the encouragement of the Editor-in-Chief, a short paper appeared in this Journal entitled "Schizophrenia; A New Approach" (18). In this paper it was noted that mescaline and adrenaline have a similar biochemical structure. It was suggested that one of the aetiological agents in schizophrenia might be a substance or substances lying between these two; with the psychological properties of mescaline but effective in con centrations nearer those of adrenaline. Dr. Harley Mason elaborated this sug gestion from the biochemical standpoint. For convenience these hypothetical substances were called, collectively, M substance. If M substance occurred in the body, it would account for the group of illnesses usually referred to as schizophrenia better than any hypothesis so far advanced. It has been the good fortune of the co-authors of that ficst paper (J, R. S. and Fl, 0,) to be able to join forces with the third author of this paper (A. H,) to test the hypoth sis. it is with the efforts of the last year that this paper is concerned.

A proposition such as this sounds simple enough to test when sketched on paper, but once it is tackled in the laboratory and the ward, many difficuhies soon appear. Money must be obtained, technical help sought, workers from other disciplines must be persuaded to give their support. When all this has been achieved, and it is no small achievement, one has not even started, First of all one must decide where to start. In the range of substances which lie between mescaline and adrenaline there are many hundreds perhaps thousands of compounds. Some of these have been made and are well known to pharma cologists, but many have found no place in medicine and are hidden away in obscure corners of the literature, or having no effect on a particular experimental animal have never been recorded in print. To make or obtain such a large number of compounds would be costly and laborious, but this work and expense would be but a tithe of the effort required to test them. For, since animals are unable to talk and so inform us of their experiences, testing must always be done on human volunteers. So, a year ago, although we had received the keenest support from the Direc tor of Psychiatric Services of the Provincial Department of Public Health, Regina, and although the Federal Department of Health and Welfare in Ottawa had secured a most generous grant for us from Dominion funds, putting us in a position to start work, there remained an unanswered question, "Where do we start?"

* One must always offer some excuse for coining a long new word, hut there is really no other satisfactory one. It is not a good word but seems to us less obscure than eideticum or phantasticum and begs the question less than "schizogen" or "schizophrenogen." As Kliiver has observed when we take these remarkable compounds we er@ter a world beyond language, so it is hardly surprising that they may be difficult to name.
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