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June 1964

Tolerance to LSD-25 in Schizophrenic Subjects: Attenuation of Effects on Pupillary Diameter and Kneejerk Threshold After Chronic Intoxication

Author Affiliations

From the National Institute of Mental Health Addiction Research Center, Public Health Service Hospital.
Formerly Chief (Dr. Chessick), Psychiatric Service No. 2, US Public Health Service Hospital, Lexington, Ky. Present address: Chief, Psychiatric Service, Veterans Administration Research Hospital, Chicago, Ill. Research Psychologist (Dr. Haertzen), NIMH Addiction Research Center. Formerly Chief (Dr. Wikler), Section on Experimental Neuropsychiatry, NIMH Addiction Research Center, Lexington, Ky. Present address: Professor, Department of Psychiatry, College of Medicine, University of Kentucky, Lexington, Ky.

Arch Gen Psychiatry. 1964;10(6):653-658. doi:10.1001/archpsyc.1964.01720240107012

The experiments here reported were designed to test the hypothesis that, unlike nonpsychotic subjects, patients with chronic schizophrenia do not develop tolerance to N,N-diethyl-D-lysergamide tartrate (LSD-25)—a hypothesis which, if confirmed, would indicate that this disorder is associated with a defect in some mechanism of tolerance to normal, but potentially toxic products of metabolism, rather than to abnormal production of some as yet unidentified toxin.

Cholden et al1 had already reported that in chronic schizophrenic patients grossly observable changes in behavior do occur after intramuscular injection of a single dose of LSD-25 (100μg total) and that such effects are no longer observed after once-daily repetition of this dose for three days or even after progressive increase of the daily dose to 500μg over a period of five days, but we were not aware of their findings until after our experiments had been completed.

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