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

Author: mycolabadmin
2/8/2023
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Summary

Researchers tested 13 mind-altering drugs on developing zebrafish to see if they cause birth defects or behavioral problems. They found that psychedelics like psilocybin and ketamine were relatively safe for developing organisms, but traditional drugs of abuse like cocaine and methamphetamine caused significant behavioral changes without obvious physical defects. The study provides important safety information for these compounds, especially for pregnant or nursing individuals considering their use for therapeutic purposes.

Background

Psychedelics have gained interest as potential therapeutic agents for neuropsychiatric disorders, but their developmental neurotoxicity has not been rigorously assessed. Safety data is limited, with few studies in developing organisms and limited compound comparisons. The paucity of data regarding potential adverse effects on early neurodevelopment is particularly concerning given that psychedelics can cross the placenta and are used by people of childbearing age.

Objective

To screen 13 psychoactive compounds of different chemical and pharmacological classes for teratological and behavioral abnormalities in larval zebrafish following acute and chronic developmental exposures. The goal was to compare the relative potential for inducing developmental neurotoxicity across a wide structural array of psychedelics and related compounds.

Results

Over half of the psychoactive compounds altered behavior without producing overt teratogenic effects. Psychedelic tryptamines and ketamine were less neurotoxic than LSD and psychostimulants. Psychostimulants (amphetamine, MDMA, methamphetamine, cocaine) and compounds affecting dopamine signaling produced significant neurodevelopmental toxicity, while selective serotonergic compounds showed minimal behavioral effects.

Conclusion

The study provides a robust reference database for comparing neurotoxicity profiles of psychedelics. Compounds modulating dopaminergic signaling produced significant neurodevelopmental toxicity, while tryptamine psychedelics and ketamine showed reduced neurotoxicity. The findings underscore the usefulness of zebrafish models for higher throughput toxicity screening of novel psychedelics.

Published in:ACS Chemical Neuroscience,
Study Type:Experimental Laboratory Study,
Source: 10.1021/acschemneuro.2c00642, PMID: 36753397