Gestational psychedelic exposure disrupts brain development and offspring behavior in mice
Despite increasing non-medical use and clinical investigation of psychedelics, the consequences of prenatal exposure remain unknown. In mice, maternal lysergic acid diethylamide (LSD; 0.3 mg/kg) crossed the placenta, appearing in embryonic cerebrospinal fluid (CSF) within minutes at E12.5 and E16.5. Within 30 minutes, LSD and other serotonergic psychedelics activated the embryonic choroid plexus via 5-HT2C, triggered apical remodeling, and increased CSF protein. A single E12.5 exposure altered cerebral cortical laminar organization and composition at postnatal day 8, and repeated dosing (E12.5 - E16.5) amplified male-biased shifts from SATB2+ to CTIP2+ neuronal identities and increased microglia. Adult offspring showed reduced prepulse inhibition (male-predominant) and rotational stereotypy. These data identify an embryo-facing interface that detects maternal psychedelics and link CSF access to enduring neurodevelopmental and behavioral consequences.