Schizophrenia and adrenaline

Editor's Column S C H I Z O P H R E N I A AND A D R E N A L I N E H E production by adrenochrome were preoccupation with inanimate obpsychologic states resembling jects, negativism, loosening of the assothose found in schizophrenia has re- ciative process, anxiety, and distraccently been reported by Hoffer, Os- tibility. mond, and Smythies of Saskatchewan. 1 Adrenoehrome is one of the numerThis observation has special signifi- ous substances with a chemical struccance in that adrenochrome is prob- ture similar to adrenaline and mesably a normal product in human me- caline. However, it does not produce tabolism. the gross physiologic effects of adrenWhen adrenochrome was admin- aline nor the clouding of consciousness istered to a number of human volun- and confusion of mescaline. teers variable mental syndromes folAdrenoehrome was discovered by lowed. Dr. Hoffer became overactive, Green and Richter 2 in 1937 who found showed poor judgment and lack of in- that it acted as a hydrogen carrier in sight. Mrs. Hoffer became severely concentrations which are physiologic. depressed and remained in this state It was present in skeletal muscle in for four days. She, too, showed lack of minute amounts. There is some doubt insight and was unable to relate her as to its presence in the human body. depression to the injection of adreuoAdrenaline is disposed oP in the chrome. The prolongation of symp- body by (1) excretion in the urine, (2) toms may have been due to an attack storage in the cells, (3) deamination of infectious hepatitis some years to form oxidizable aldehydes, (4) earlier. esterification of the phenol hydroxyls, Another subject, Dr. Osmond, re- and (5) quinone formation to adrenosponded to an injection of adreno- chrome. Interference with any of the chrome with visual hallucinations : first four mechanisms may lead to an The ceiling changed color, the lighting increased production of adrenochrome. appeared brighter, brightly colored Woodford~ has shown that, when patterns of dots appeared when the adrenochrome enters the brain cells, it eyes were closed, which resolved them- inhibits markedly the intermediary selves into fishlike shapes. The Ror- metabolism of carbohydrates. To demschach cards, which were familiar to onstrate that adrenochrome can cross the subject, were changed in an ex- the blood-brMn barrier, electroencephtraordinary manner. They were dif- alographic tracings were made. It ferent in texture and in bas relief ap- was possible to demonstrate changes pearance and the shapes were strange in epileptics with normal electroenand amusing. This subject felt cut off cephalograms within a half hour after from people but he was not unhappy. administration and the experimenters He speculated as to whether he was are now using adrenochr0me routinely really a person or merely a plant or a in establishing the diagnosis of epistone. Interest in human beings dwin- lepsy since it so clearly brings out the dled. Changes noted by his co-workers epileptic activity. 133

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Adrenoehrome inhibits hexokinase under anaerobic conditions. ~ I t also inhibits the aerobic oxidation of glucose and pyruvate. The observations of Heifer, 0smond, and Smythies suggest that a schizophrenia-like syndrome can be produced in h u m a n beings by the administration of a substance, adrenochrome, which probably oeeurs in the human body. Adrenoehrome, unlike adrenaline, can cross the blood-brain barrier where it interferes with aerobic and anaerobic respiration. Rinkel, Hyde, and Solomon G have been using the recently discovered diethylamide t a r t r a t e of d-lysergie acid (LSD) to in~uee psychotic conditions. I t is their view t h a t LSD acts by int e r f e r e n c e somewhere within t h e adrenaline cycle. These workers were unable to produee psychotic symptoms i n themselves or in volunteers with commercial adrenochrome, nor have mental alterations been observed in surgical patients in whom it has been used because of its strongly hemostatic effect. They suggest t h a t the results obtained b y I-Ioffer, Osmond, a n d

S m y t h i e s were not due to adrenochrome but, possibly, to adrenoxin, a f u r t h e r oxidation product o f adrenaline which m a y have been present in the impure p r e p a r a t i o n u s e d . A d r e n o x i n is an unstable metabolite of adrenaline, obtained by prolonging the oxidation of adrenaline beyond the a d r e n o c h r o m e level. The evidence of various workers p o i n t s to a relationship between schizophrenia and the metabolism of adrenaline. It.B. REFERENCES I. Hoffer, A., Osmond,

H., and Sraythies, J.:

Schizophrenia: A New Approach. II. Result of a Y e a r ' s Research, J. Ment. Se. 100: 29, 1954. 2. Green, D. E., and Richter, D.: Adrenaline and Adrenoehrome, Bioehem. J. 31: 596, 1937. "3. Baeq, Z . M . : Metabolism of Adrenaline, Pharm. Rev., P a r t I I of the April, 1949, issue, J. PharmaeoI. & Exper. Therap. 95: 1, 1949. 4. Woodford, V.: Private communication to be published. Quoted by tIoffer e t al.a 5. Meyerh0f , O., and Randall, L. O. : Inhibitory Effects of Adrenoehrome on Cell Metabolism, Arch. Bioehem. 17: 171, 1948. 6. Rinkel, 2~[., Hyde, R. W., and Solomon, H. C.: E x p e r i m e n t a l Psychiatry. III. A Clinical Concept of Psychosis, Dis. Nerv. System 15: 2,59~ 1954.

F L U O R I D A T I O N FOR T H E P R E V E N T I O N OF D E N T A L CARIES E W proposed public health measF ures have been the subject of so much c o n t r o v e r s y and acrimony as the fluoridation of community w a t e r supplies to p r e v e n t dental caries. Despite the endorsement of the program by dental, medical, and health scientific organizations, vociferous opposition exists. Certain facts are clear and definite. In communities where there is an appreciable n a t u r a l fluoride content in the w a t e r the extent o f dental caries is only one-third of t h a t f o u n d

in communities where fluorides are absent, iViany examples could be quoted. An excellent one is two cities in n o r t h e r n Illinois. In Galesburg, where the n a t u r a l fluoride content of the w a t e r is 1.8 parts per million (ppm), a s u r v e y of children 12 to 14 years of age showed 201 carious defects per 100 children, while in Waukegan, where the n a t u r a l content is 0, the e x t e n t of caries reached 810 per 100 children. These children had been living and b r o u g h t up in communities where the public w a t e r supply had