MAR 18 1964 LIBRARY Ramasey County Medical s ST. PAUL, MINN, volume 25 number 2 february 1964 A Practical Journal on Psychiatry and Neurology (Conrixts oN Pace 66) Published Monthly by: PHYSICIANS POSTGRADUA 1 Broadway - New York 1, Entared as second-class matter at the Post Ofn at New York, X. ¥| Volume XXV MARCH 1964 Number 3 DISEASES fe Nervous System | Contents NON-SPECIFIC FACTORS IN TREATMENT Gilbert Honigteld ONEIROPHRENIA- ENTITY OR ENIGMA? James , Reardon YOU CANNOT BE A DRUG ADDICT WITHOUT REALLY TRYING Bernard W. Casselman COMPARISON OF DIAZEPAM, CHLORPROTHIXENE AND CHLORPRO- MAZINE IN CHRONIC SCHIZOPHRENIC PATIENTS George A. Maculans CLINICAL TRIALS WITH AMITRIPTYLINE AND PERPHENAZINE ‘AMONG PSYCHIATRIC OUTPATIENTS. Blaine E. McLaughlin, Frank Ryan, and Trudy Drucker USE OF METHANDROSTENOLONE IN CHRONIC SCHIZOPHRENIC PATIENTS R.V. Heckel, Dorothy T, Clark, M. Berman, and R.C. Hall ‘THE ADRENOCHROME THEORY OF SCHIZOPHRENIA: A REVIEW A. Hotfer CLINICAL EVALUATION OF J8-329 (DITRAN) H.K. Davis, HLF. Ford, J.P. Tupin, and A. Colvin TREATING SMOKING HABIT BY DISCUSSION AND HYPNOSIS Ferris M, Moses BOOK REVIEWS William W, Zeller, Editor Titus ML Mares, ALD, Texas MANAGING EDITOR George Bingete, BS. LLB. York, New York ASSOCIATE EDITON David J. tmpastato, 3.0. Francis Franiin Hamilton Ford, MD. Walter Freeman, 3.D_— AL Hauser, MD. YEARLY SUBSCRIPTION $10.00 Foreign Subscription $11.501964 DISEASES OF THE NERVOUS SYSTEM 173 The Theory of Schizophrenia: A Review A. Horrer, Pu.D., M.D, History In 1952, Osmond and Smythies* report- ed that normal subjects who had ingested mescaline developed a psychological ex- perience which was very similar to the psychological changes reported by pa- tients suffering from the disease schizo- phrenia, Mescaline is chemically similar in structure to adrenaline. This observa- tion had been made use of in psychiatric research by De Jong", but Osmond and ‘Smythies suggested that a chemical with the psychological properties of mescaline and deriving from adrenaline might be present and be a cause of schizophrenia. Dr. Osmond joined me in Saskatchewan in 1951, and within a few months we be- gan our research, Adrenochrome was then the only known derivative of adrenaline and it seemed logical to study it, Later, we hoped to study other adrenaline deriva tives. In 1952 with Dr. Osmond, I outlined our adrenochromé hypothesis to the De- mentia Praecox Committee, Scottish Rite Masons, in New York, By 1954, Hoffer, ‘Osmond and Smythies were able to report that adrenochromé had a marked effect on the central nervous system of man. It pro- duced psychological changes in the first four volunteers to whom it was given. Dr. Osmond noted changes in visual percep- tion, changes in thought, apathy, uncer- tainty, and I noted in him a marked change in personality which I had not witnessed before or since. I myself ex- perienced mild visual changes and then, after the second injection, a period of severe depression of a psychotic nature, which lasted over two days. Finally, we reported that, injected into epileptic pa- tients, produced a marked change in the electroencephalogram.” * From the Paychiatrie Research Division, Psy- chiatric Services Branch, Department of Public Health, Saskatshewan. ‘Thus, in 1954, we first widely publicized our fidrenochromé theory. Smythies was associated with us for a brief period in 1952, when he left us, Later, Smythies publicly dissociated himself from the adre- nochrome hypothesis. Scientific Approach We hypothesized that there was some abnormality in the metabolism of adreno- chrome in schizophrenic patients, Early in our work, we believed that there was simply too much adrenochrome present. This could be the result of an increased production or a decreased destruction, but both factors probably were operative Later on, as our knowledge of the chem- istry of adrenochrome improved, we real- ized that the pathway taken by the body in degrading adrenochromé might be equally important, Our present theory of schizophrenia is that in schizophrenic pa- tients, fadrencchromd is converted into adrenolutin, whereas in people who are not ill with schizophrenia, most of the is metabolized into a dihy- droxy-N-methyl indole, This shift in the metabolism of adrenochrome could be due to some defect in enzymes which convert- ed adrenochroméd into the non-toxic dihy- droxy indole. The adrenochromé theory is not antagonistic to the serotonin or tarax- ein work. The original impetus for Health's isolation of taraxein came from the early adrenochrome hypothesis. Even- tually the role all these chemicals play will be worked out, They may well be linked to each other. The proof for this hypothesis therefore falls into two main areas, First, it must be shown that is active when given to animals and can produce psychological changes in man, and that these are similar to changes found in schizophrenia, Second, it must be shown is present in the bodym sos DISEASES OF THE NERVOUS SYSTEM a tnd even more, that it is present in in- actions. Weckowis." in a very careful saceiceaaees Naver, - hain obesialon’ te taeda Creed concentration cleopheni pe sdy,foud hat REROREORE re L0 ported sme € te bx periments ova, pertape tyramine ce tye, tt tents when they are ill and decreased in rats in conditioning experiments, de- human subjects, These experiments were source, Neverthcles, the adrenochrome roncentration when they recover. creased. rate of learning (acquisition a ee tere Oat tre waeeaten “The reearch work now published up- TL ala markedly increased extinction of | ¢| ‘Afri out double wind, wong, to 3) ports both ruppositions, and It now ems the conditioned avoidance respons. Using | 5] tammontvonns mtsenani, Tht Levey corre tome only a matter of time before the bar pressing experiments in a Skinner | 3] tt nulfersd ot he perceptual Chatgey 4 theory of schizophrenia must acount Uzenochrome theory is generally accepted box, there was significant reduction in Te emaaE uty, inteane ann. for stene 6 tho eiieal und biochemical ‘sone useful biochemical explanation for bar pressing for food or water. Adreno- rite tnins ome haliecinations, changes in echaophrena, If we postulate cchisophrenia, Of course there must be chrome hed no eflsct on areusal or drive ‘both visual and auditory, They saw fdrenochrome and adrenclutin alter that ‘ther biochemical hypotheses as well. and on motor performance en saa thought cad marked changes Portion of, the entral mervous tem . ‘Aarenodtramé fas alo been used to ‘the word assosiation tex. The quantity which deal with perception, tin onal Peychological Perpcennencept potreredinsr inane} cf disturbed amociations was similar to‘ account for many of the clinical ‘The theory suggests that HAEEEOERORE the’ cleetroencephalogram were atch. ‘hone found in schizophrenic patienta changes" and one of its derivatives, adrenouti sre Changes have also been chnerved in cats her LSD-25 or mescaline did thin. _AUEeROEHFGHE has the following bio- tox chemicals and that 2, 3 diydroxy- hen thee compound were placed in the ‘There were also changes in mood, Asa chemical activity: (I) Tt is readily poly ¢-amethyl indole ie not brain ventricles or when they were g1Ve0 result, they ‘concluded their work fully. meried to darkly colourel pigments, and Dinydroxy-N-methyl indole is indeed jntraperitoneally. It is interesting. that ‘corroborated our earlier Sashatchewan this could account for the ineeased Pi non-toxic for animals and man, Hoffer and when eats were pretreated with an inac- ‘work. There ir no further doubt adreno- mentation of some patieta. (II) Adre Onmond™ have given thia substance to ye quantity of Wlyeergie acid ethyl: ‘chrome isan active paychotomaimetic nochrome is a strong peison of cellular neatly 100 people, most of them patients. mide there was a ten-fold potentiation of ‘agent. {mitosis and should therfore produce an Some subjects have taken it regularly @& the eifet of adrenoltin™ iteration of all tinue where growth is fan ant-ension substance for orer three eee rapid" This may produce reduced rate Years, At no time have we seen any torie The only work with dogs was reported Several compounds are present in the of'tisme repair and s0 account for the Teactions, However, some of the commer- {rom the Institute of Paychiatry, Academy] | body which can be converted into adreno- jncreased incidence of tuberculosis in ac al preparations with which we have Of Medical Scences, USSR Kuchino™ re- ‘chrome oF similar compounds, These in- zophrenie patients" (III) AGFERGERTORS “worked have produced some toxic effects. Ported that 1 mg/kg. of adrencehrome ‘clude tyrosine, tyramine dopamine," nora- has antihistamine properties, and {appears posible that certain impurities ablished conditional reflexes in dogs. | dr | drenaline and adrenaline. The question is, can account for decreased. incidence inthe preparation ean be tox. Braines™ found that dogs made anxious Which of these is the major substrate. A of" allergies in achizphrenia an ‘A complete review ofthe peychological «Xperimentally were much more mnsitive | m | number of workers have auggeated adre- their" Increased resistance to. surgical properties of adrenochrome an adreno- ‘0 Sdnenochrome! 3c] mochrome is formed and another group shock? (IV) Arsene ros co Jutin has appeared” " (SSRSEEGGD han 0 ma ve claimed to have * Recently, ie acid and dehydroascorbic acid to. 8 . omega wits | AD] Altschules"="*"="0" and his colleagues non-ritamin substance " Thi cam account tis | have found an aminochrome, probably for the inreased demand for ascorbic acid a | adrenolutin, is present in high concentra- by schizophrenic patients" and for some tic | tion inthe red cells of the blood and in therapeutic success achieved with ascorble at | rine of schizophrenic patients" About seid (V) Adrenochromd san inhibitor of 80 } 80 percent of all the schizophrenics tested choline caterase- and thie could account ha | had thin Altschule™ hun suggested that for the increase in acetylcholine in ach thin assay for aminochromes be used as a aophrenie maliva, (VI) Adrenochrome in- ta | basis for diagnosing a rew disease which terfeen with carbohydrate metabolism of he | he has named hyperaminochromia. Most cells" and inhibits eynapt: transmission. ct | of his cases of hyperaminochromia are Tt ia not surprising thers In some toxic ct | Glinicany schizophrenic. ‘effect om the eentral nervous system. ‘Thus, our second supposition derived The adenachromd theory thus accounta tm | trom the edethochraiié theory is confim- reasonably well for the biochemistry and cd | cd. But the exact source is not known. physiology ‘of schizophrenia, and like ‘Ac | According to Altschule the adrenolutin. theories in other felds of medicine, may ike aminochrome In derived from tyro- lead to the final defeat of this great dis- sine, but T ave suggested adrenaline iw a ease, T have not touched upon the ey: 20 | source. We have work underway to locate chological theories which deal with the176 psychological content, nor with interper- sonal and cultural ideas which deal with the consequences of this disease. The adre- nochrome theory has given us some leads into these interesting problems which we are now examining. Conclusion The strength of the adrenochrome hypo- thesis depends upon two chief findings. One, that adienochrome is a psychotomi- metic compound, Two, that its presence in the body is related in time to the elini- eal disease. The evidence for both is powerful and increasing in strength. Re- search psychiatrists must hereafter help gather the data which will finally show whether it is a correct hypothesis, BIBLIOGRAPHY A B 4. 2 3. a 4 2 Do Pers, Laboratory ‘of Beperimental Pa: Enclogy, nettle ‘of Poychatry, Ace. demy of Sciencee, Moscow. Chea cat al B00)” Act, Nore 5a 5, Bade, N. R. (1964). PRD. Thesin, Grad- tate ‘School, ‘Unie. of Baak. Saskatoon, Canada © Grot. 8. (1980). Acti. Mere. Buper. 2, 7. Grof, 8, of al (1961). Abstract of International Congress Payehiatry, Mon: val Je, rot, 8..fet al (1961). Acti, Nerv, Bu- ft al, (1961). Actie, Were. Super. 3, 10, Hoffer, A. 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