Which Came First? Utility of Preclinical Models in Cracking the Chicken-or-Egg Relationship between Cannabis Use and Schizophrenia
Current Addiction Reports February 27, 2026 Amanda C. Lee, Jibran Y. Khokhar
Cannabis use is linked to schizophrenia, especially in vulnerable people. Preclinical rodent models help clarify this relationship by allowing controlled experiments that are impossible in humans. Recent studies use advanced paradigms, including translationally-relevant rodent models and ecologically valid cannabis administration routes, to simulate human use patterns and vulnerability. These models show that cannabinoid exposure can alter schizophrenia-like behaviors and neural effects related to hyperlocomotion, sensorimotor gating deficits, social withdrawal, and anhedonia. The route of administration, dose, and type of cannabinoid shape these outcomes. Such findings identify periods of heightened vulnerability and inform prevention and intervention strategies.