Adolescent cannabinoid exposure delays development of prefrontal cortex perineuronal nets and inhibitory interneurons.
Neuroscience March 23, 2026 Eliza Jacobs-Brichford, Rachel M. Donka, Amy W. Lasek et al.
Inhibitory signaling in the prefrontal cortex matures during adolescence, a critical period when parvalbumin-positive interneurons are surrounded by perineuronal nets. The endocannabinoid system helps regulate excitatory-inhibitory balance. Treating male and female rats with the synthetic cannabinoid WIN 55,212-2 from postnatal day 35 to 45 reduced perineuronal nets and delayed the emergence of parvalbumin-positive cells. These changes occurred earlier in females but persisted into adulthood in males, causing disinhibition of prefrontal cortex neural activity in awake adult animals, more strongly in males. Cannabinoid exposure during adolescence may alter perineuronal net development, leading to lasting functional changes in inhibitory signaling and potentially impairing executive control of behavior.