Effect of Cyanide and Sodium azide on fish surfacing reaction

Weiss and colleagues tested the hypothesis that LSD acts by anoxia and asphyxia. They added Siamese fighting fish to water containing the oxidase inhibitors, potassium cyanide (KCN) and sodium azide. KCN and sodium azide affected Siamese fighting fish in a way which was very similar to LSD, suggesting that LSD might normally work by preventing oxygen uptake. Figure 2 (below) shows the fish surfacing reaction for 1 ug LSD (left) and 1 ug KCN (middle). There is no surfacing reaction in the H2O control (right).

From LSD fish

It was interesting that KCN was nearly as potent as LSD, since I am unaware of any other drugs, with the exception of other hallucinogens, that cause LSD-like behavior in the same concentration range as LSD in a biological assay. There were some differences between KCN and LSD, for example fish recovered more quickly from 1 ug/mL KCN than 1 ug/mL LSD. The figure on the right is the KCN surfacing curve plotted on the LSD surfacing curve.

From LSD fish

The authors observed that CO2 poisoning itself causes a nose up-tail down reactions in fish. When carbon dioxide was permitted to accumulate in the absence of renewed oxygen, all the fish assumed the nose up-tail down position in several hours. Thus inhibition of O2 oxidation was a general feature of the fish intoxication produced by LSD, KCN, and sodium azide.

"A decreased oxygen supply with simultaneous prevention of accumulation of carbon dioxide resulted in the nose up-tail down position similar to that for LSD in several hours, the fish remaining alive." (B. Weiss, 1958)

A concentration of methylene blue of 100 ug/mL also caused a nose up-tail down reaction. There were similar results with gentian violet and Bindschedler's green.



Reference

WEISS B., H. A. ABRAMSON and M. O. BARON. (1958). Lysergic acid diethylamide (LSD-25). XXV. Effect of potassium cyanide and other oxidase and respiratory inhibitors on the Siamese fighting fish. AMA Arch.Neurol.Psychiatry. 80, 345-350.