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February 1958

Lysergic Acid Diethylamide (LSD-25) Antagonists: II. Development of Tolerance in Man to LSD-25 by Prior Administration of MLD-41 (1-Methyl-d-Lysergic Acid Diethylamide)

Author Affiliations

Cold Spring Harbor, N. Y.

From the Biological Laboratory, Cold Spring Harbor, and the Research Division, Central Islip State Hospital.

AMA Arch NeurPsych. 1958;79(2):201-207. doi:10.1001/archneurpsyc.1958.02340020081015

A. Introduction  It has been shown1,2 that 2 mg. of crude beef brain extract per milliliter of water blocks the usual effect of 2μg of LSD-25 per milliliter in the outside liquid on the Siamese fighting fish.* The experiments to be reported here are the study of a blocking effect probably produced by another mechanism: the development of tolerance3 to LSD-25 in man by the prior administration for a period of days of a compound similar to LSD-25. This compound, 1-methyl-d-lysergic acid diethylamide (MLD-41), produces in man reactions indistinguishable from LSD-25 but has a higher reaction threshold. It will be shown on the basis of our data that MLD-41 affects both the Siamese fighting fish and man in a manner similar to LSD-25. However, there are important differences; in the fish it is about 1/10 as effective as LSD-25, whereas it is approximately 1/3 as effective in man.

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