Barry Blackwell and Kanellos Charalampous: Kanellos Charalampous: Confronting the Zeitgeist

Comment by Thomas A. Ban


            I read with interest your biography and noted your research related to the “pink spot”. It brought back memories from the 1960s, about a time when I was coordinating the Canadian Mental Health Association (CMHA) Collaborative Studies on Nicotinic Acid in the Treatment of Schizophrenias (Ban 1971 a, b; Ban and Lehmann 1970).    At the time the CMHA Collaborative Studies were designed, in the early 1960s, psychotoxic metabolites of catecholamines and indoleamines were implicated as the culprit for schizophrenia and our intention was to test the hypothesis that the presence of one of these metabolites, 3,4-dimethoxyphenylethylamine (DMPEA), in the urine of schizophrenic patients was a predictor of favorable outcome to treatment. The idea was that administration of nicotinic acid that converts into nicotinamide, a methyl acceptor, will prevent the formation DMPEA, a dimethylated dopamine.  Yet, by the time we were ready to test this hypothesis, in the late 1960s, we decided not to proceed, in light of findings like yours, which conclusively demonstrated that DMPEA has no psychotoxic effects (Charalampous 1966; Friedhoff and Hollister 1966; Hollister and Friedhoff 1966). The story of DMPEA began, in 1934, with Noteboom’s discovery that DMPEA produced experimental catatonia in rats. It continued, in 1952, with Harley-Mason’s implication that DMPEA, formed in the body, is the culprit of schizophrenia (Osmond and Smythies 1952) and culminated, in 1962, with Friedhoff and Van Winkle’s detection of a “pink spot” with paper chromatography in schizophrenic urine and determination of the chemical responsible for the “pink spot” as DMPEA.

            In spite of the demonstration in the mid-1960s that DMPEA has no psychotoxic effects, the controversy about the “pink spot” continued well into the early 1970s (Ban 1973).


Ban TA. Nicotinic Acid in the treatment of schizophrenia. Introduction. Toronto: Canadian Mental Health Association; 1971a.

Ban TA. Nicotinic Acid in the treatment of schizophrenia. Complementary Report A. Toronto: Canadian Mental Health Association; 1971b.

Ban TA. Recent Advances in the Biology of Schzophrenia. Springfield: Charles C. Thomas; 1973.

Charalampous KD. Clinical and metabolic studies of KD. Clinical and metabolic studies of B-phenylethylamines- mescaline and ß-3, 4 dimethoxyyphenylethylamine. Excerpta Medica Foundation; International Congress Series No. 150, 1966; 2377-2379.

Friedhoff AJ, Hollister LE.  Comparison of the metabolism of 3, 4-dimethoxyphenylethylamine and mescaline in man. Biochem Pharmacol 1966; 15: 269..

Friedhoff AJ, Van Winkle. Isolation and characterization of a compound from the urine of the schizophrenic. Nature 1962; 194: 897-8.  

Hollister LE, Friedhoff AJ. Effect of 3, 4-dimethoxyphenylethylamine in man. Nature 1966; 210: 1377. 

Osmond H, Smythies J. Schizophrenia: a new approach. J Ment Sci 1952; 98:309-15.


Thomas A. Ban

August 18, 2016