Gestational psychedelic exposure disrupts brain development and offspring behavior in mice.
Ya'El Courtney, Josephine M Anderson, Christian Lagares-Linares, Cody J Wenthur, Maria K Lehtinen
bioRxiv : the preprint server for biology September 30, 2025 preprint DOI: 10.1101/2025.09.30.677638 via PubMed
Summary
AI-generated from the abstractIn mice, the psychedelic drug LSD crosses the placenta and enters embryonic cerebrospinal fluid within minutes. A single dose during pregnancy alters the organization of the cerebral cortex in the offspring, and repeated doses shift the balance of neuron types and increase microglia. Adult offspring, especially males, show reduced prepulse inhibition and rotational stereotypy. These findings identify a mechanism by which maternal psychedelic exposure can lead to lasting changes in brain development and behavior.
Study at a glance
| Characteristics | Experimental study |
|---|---|
| Population | Mice |
| Dose | 0.3 mg kg -1 |
| Duration | Single dose at E12.5 or repeated dosing from E12.5 to E16.5; outcomes assessed at postnatal day 8 and in adulthood |
| Keywords | Maternal psychedelic exposure Prenatal hallucinogen exposure Gestational LSD Use Maternal substance use Neurodevelopmental impacts |
| Key finding | Maternal LSD exposure in mice alters fetal brain development and leads to lasting behavioral changes in adult offspring, including reduced prepulse inhibition and rotational stereotypy. |
Abstract
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 -1 ) 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 induced a 5-HT 2 C agonist-like response in the choroid plexus, triggering apical remodeling and increasing 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.