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Prenatal CB1 Receptor Knockdown in Mice Distorts Cortical Development and Behavior

Findings raise questions about prenatal cannabis exposure but do not establish effects in humans.

Overview

  • Peer‑reviewed results in the Journal of Neuroscience were reported September 22, 2025 by a team led by Ismael Galve‑Roperh at Complutense University of Madrid.
  • Researchers transiently reduced CB1 receptor expression using in‑utero siRNA electroporation at embryonic day 14.5 to target developing prefrontal cortex neurons.
  • The prenatal manipulation arrested neuronal migration and created ectopic deep‑layer neurons, disrupting normal cortical lamination.
  • Recordings showed the ectopic neurons were less excitable, and gene‑expression profiling highlighted alterations in development, migration, neurotransmission and cytoskeletal pathways with overlap to risk genes including ZBTB20.
  • Adult offspring exhibited persistent social interaction impairments and motor deficits, indicating long‑term behavioral consequences of prenatal CB1 signaling disruption in mice.