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Summary The effect of pH on the transport of lysergic acid diethylamide (LSD 25) and of methysergide has been studied in both Siamese fighting fish and goldfish. Two methods have been employed to study the transport of these drugs. In one method, the fish were immersed in a solution of the drug, thus providing an essentially unlimited supply of the drug in the outside liquid during the course of the experiment. In the second method, the fish were dipped for a much shorter period and then observed after the excess drug had been washed off. If has been found that the pH of the outside liquid, in both methods, is a major factor controlling the transport of LSD 25 and methysergide across the gills. Between pH 5.0 and pH 5.7, the surfacing reaction of the fish is diminished, with maximum blocking occurring at pH 5.0, the blocking effect diminishing to zero at pH 5.8. The data are discussed in connection with the permeability of the blood brain barrier of the nervous system to psychotomimetic drugs.

A simplified method of studying the surfacing reaction of goldfish to hallucinogens is described. Goldfish weighing up to three grams are injected intracranially. Employing this method, d-lysergic acid diethylamide (LSD-25), d-2-acetyl lysergic acid diethylamide (ALD-52), 1-methyl d-lysergic acid butano-lamide (UML-491), and 5-methoxy dimethyl tryptamine (5-MEO-DMT) were found to be as pharmacologically active as previously noted in fish and in man. The relationship of these drugs to their anti-serotonin activity is of particular interest to the allergist because of the way in which the congeners and derivatives of LSD block the action of serotonin on smooth muscle.

Serotonin, when injected intracranially and intraabdominally into goldfish produces the surfacing reaction typical of hallucinogenic compounds active in man. It is suggested that serotonin disorders in the brain in man might be connected with the schizophrenias.