Developmental Neurotoxicity Screen of Psychedelics and Other Drugs of Abuse in Larval Zebrafish (Danio rerio)

In recent years, psychedelics have garnered significant interest as therapeutic agents for treating diverse neuropsychiatric disorders. However, the potential for these compounds to produce developmental neurotoxicity has not been rigorously assessed, and much of the available safety data is based on epidemiological studies with limited experimental testing in laboratory animal models. Moreover, the experimental safety data available thus far have focused on adult organisms, and the few studies conducted using developing organisms have tested a limited number of compounds, precluding direct comparisons between various chemical scaffolds. In the present study, 13 psychoactive compounds of different chemical or pharmacological classes were screened in a larval zebrafish model for teratological and behavioral abnormalities following acute and chronic developmental exposures. We found that the psychedelic tryptamines and ketamine were less neurotoxic to larval zebrafish than LSD and psychostimulants. Our work, which leverages the advantage of using zebrafish for higher throughput toxicity screening, provides a robust reference database for comparing the neurotoxicity profiles of novel psychedelics currently under development for therapeutic applications.

Automated summary

In recent years, there has been a growing interest in using psychedelics as therapeutic agents for neuropsychiatric disorders. However, the potential developmental neurotoxicity of these compounds has not been thoroughly assessed, and the available safety data is limited. This study used a larval zebrafish model to screen 13 psychoactive compounds and found that tryptamines and ketamine were less neurotoxic to the larvae compared to LSD and psychostimulants. This research provides a valuable reference database for evaluating the neurotoxicity of novel psychedelics under development for therapeutic purposes.