Which Came First? Utility of Preclinical Models in Cracking the Chicken-or-Egg Relationship between Cannabis Use and Schizophrenia

Summary

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.

Study at a glance

Abstract

Purpose of Review The association between cannabis use and schizophrenia is a growing public health concern, particularly in vulnerable populations. This review synthesizes insights from recent studies to investigate how preclinical rodent models can help clarify this relationship. Recent Findings Increasingly advanced paradigms have been developed, including various translationally-relevant rodent models and ecologically valid cannabis administration routes, to better simulate human use patterns and vulnerability, as well as studies combining both genetic and environmental risk factors. Together, these models show that cannabinoid exposure can alter schizophrenia-like behaviours 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. Summary Preclinical rodent models allow for controlled investigations that would be impossible and unethical in human studies. Recent models have contributed to our understanding of how genetic, pharmacological, and neurodevelopmental factors interact with cannabinoid exposure and neural circuitry to produce schizophrenia-relevant outcomes. Such findings are critical for identifying periods of heightened vulnerability and informing evidence-based prevention and intervention strategies.