Psychedelic-induced behavioral and developmental effects on zebrafish: a systematic review

Psychedelics are mind-altering substances that have shown promising effects in the treatment of neuropsychiatric disorders owing to their antidepressant, anxiolytic and antiaddictive effects. However, data on their developmental toxicity is scarce, which might hinder its therapeutic suitability, and preclinical data on their behavioral effects is mainly restricted to rodents. In this context, zebrafish emerge as vertebrate model, since it shows well conserved genetic, neurodevelopment, molecular and physiological pathways that are comparable to humans. Additionally, high fecundity, clear embryo visualization, fast development and good nervous system homology make it an interesting model in assessing developmental toxicity and behavior. Thus, we conducted a systematic review of the articles which evaluated these parameters after psychedelic exposure. Thirteen articles were included of which nine focused on adult behavioral alterations and four on developmental toxicity. Substances used included ayahuasca, dimethyltryptamine (DMT), ibogaine, lysergic acid diethylamide (LSD), methylenedioxymethamphetamine (MDMA), mescaline, noribogaine, psilocybin and psilocin. Overall, psychedelics did not elicit morphological abnormalities in embryo-larvae, although ayahuasca induced edemas and increased mortality at high concentrations. Ibogaine, MDMA and LSD were associated with locomotor impairments after exposure during development. DMT, psilocybin and psilocin elicited an anxiolytic effect on larvae, while LSD, MDMA, mescaline and noribogaine reduced anxiety in adult fish. Altogether, psychedelics present a safe toxicological profile at low concentrations in zebrafish, but it is yet unclear whether they induce offspring's neurodevelopment deficits. Further studies are warranted to elucidate the extent of these adverse effects and if they persist during development.