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Isbell H, Fraser HF, Wikler A, Belleville RE. 
“Tolerance to diethylamide of lysergic acid (LSD-25)”. 
Fed. Proc.. 1955;14:354.
Abstract
There is practically no information concerning chronic intoxication with the diethylamide of lysergic acid (LSD-25). It was noted that when former morphine addicts were given 1 or more doses the degree of LSD-effect declined rapidly. Eleven patients were given 10 ug, increasing to 30 ug of LSD orally twice daily for 3 days. On the 4th day, 75 ug of LSD induced only mild mental effects. After 3 days of placebo administration, 75 ug of LSD induced marked to severe mental effects. In another experiment, administration of 20 ug of LSD, increasing to 75 ug once daily, also induced a high degree of tolerance to the mental effects. In 12 patients, pupillary size, amplitude of knee jerk and systolic blood pressure were measured. Mental effects were gauged by means of a questionnaire. These patients received LSD once daily for 7-42 days. In 5 cases, the dose was increased from 50 to 180 ug of LSD daily; in 6 cases, dose was maintained at 1-2 ug/kg orally daily; 1 patient withdrew from the experiment after 9 days. In all patients, tolerance to all the effects measured was evident in less than 7 days. Once tolerance was developed, amounts of LSD 4 times as great as the doses to which the patients were tolerant were not as effective as the standard dose prior to chronic administration. Tolerance was completely lost 3 days after discontinuation of LSD.
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