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Behavioral Phenotyping and Metabolomic Comparison of Chemically Synthesized Psilocybin and Psychedelic Mushroom Extract in a Zebrafish Depression Model

Summary

Researchers compared chemically made psilocybin with whole mushroom extract in zebrafish to test for depression-like effects. Both treatments reversed depressive behaviors and produced similar changes in brain chemicals, though the mushroom extract showed more neurotransmitter precursors. This study demonstrates that zebrafish can be useful models for studying how psychedelics might help treat depression.

Background

Psilocybin research in depression has primarily used chemically synthesized psilocybin, but psychedelic mushrooms produce additional tryptamines that may enhance neuroplastic effects. Previous rodent studies showed psychedelic mushroom extract had stronger and more prolonged antidepressant effects than synthetic psilocybin.

Objective

To establish a zebrafish depression model and compare the effects of chemically synthesized psilocybin and psychedelic mushroom extract using behavioral phenotyping and whole brain metabolomics analysis.

Results

Both psilocybin and mushroom extract groups showed behavioral phenotypes similar to control non-stressed fish, with decreased thigmotaxis and normalized locomotor parameters compared to vehicle-treated stressed fish. Metabolomic analysis revealed increases in GABA, Vitamin B6, glutamine and NADH with decreased xanthosine in both treatment groups, with mushroom extract showing more neurotransmitter precursors than synthetic psilocybin.

Conclusion

Psilocybin and psychedelic mushroom extract administration reversed depression-like behaviors in the zebrafish model with comparable effects. Metabolomic evidence suggests neuroplastic mechanisms, and zebrafish models show promise for psychedelics research.
  • Published in:International Journal of Neuropsychopharmacology,
  • Study Type:Experimental Study,
  • Source: 10.1093/ijnp/pyae059.254
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