Lysergic Acid Diethylamide (LSD-25) Antagonists

A compound called 1-methyl-d-lysergic acid diethylamide (MLD-41), chemically similar to LSD-25, produces reactions in both Siamese fighting fish and humans that are indistinguishable from those of LSD-25, but with a higher reaction threshold. In fish, MLD-41 is about one-tenth as effective as LSD-25, while in humans it is about one-third as effective. Prior administration of MLD-41 for several days induces tolerance to LSD-25 in humans, suggesting a different blocking mechanism than that seen with crude beef brain extract.

Study at a glance

Abstract

A. Introduction It has been shown1,2that 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 tolerance3to 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.