ArticleMolecular psychiatry2026
Psychedelic 4-AcO-DMT attenuated looming-induced freezing behaviors by activating PrL
Article in Molecular psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Psychedelics modulate emotion and cognition, yet the underlying mechanisms remain unclear. Given the ability of psychedelics to induce visual hallucinations, we employed the looming model-a visual threat assay that combines visual stimulation with innate fear-to investigate the effects of psychedelics. Unexpectedly, 4-acetoxy-N,N-dimethyltryptamine (4-AcO-DMT), a psychedelic compound that acts as a prodrug of psilocin and exhibits comparable central nervous system effects to psilocybin, significantly reduced looming-induced freezing behavior compared to R/S-MDMA, without eliciting overt hallucinogen-like effects under the current experimental conditions. This anti-fear effect was independent of β-arrestin 2 signaling and visual function, but associated with decreased innate fear emotion. We identified that 4-AcO-DMT activates CaMKIIα neurons in the prelimbic cortex (PrL) via 5-HT
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