Which Came First? Utility of Preclinical Models in Cracking the Chicken-or-Egg Relationship between Cannabis Use and Schizophrenia
Amanda C. Lee, Jibran Y. Khokhar
Current Addiction Reports February 27, 2026 DOI: 10.1007/s40429-026-00714-6 (opens in new tab)
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Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Population | Preclinical rodent models |
| Topics | Cannabis |
| Keywords | Rodent model Schizophrenia Preclinical Psychosis Circuitry |
| Key findings | Preclinical rodent models show that cannabinoid exposure can alter schizophrenia-like behaviors and neural effects, with outcomes shaped by route of administration, dose, and type of cannabinoid. |
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.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cites 26
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- The Effects of Peripubertal THC Exposure in Neurodevelopmental Rat Models of Psychopathology International Journal of Molecular Sciences February 15, 2023
- The Relationship Between Cannabis, Cognition, and Schizophrenia: It’s Complicated Current Topics in Behavioral Neurosciences 2022
- Multi-level therapeutic actions of cannabidiol in ketamine-induced schizophrenia psychopathology in male rats. Neuropsychopharmacology December 1, 2024
- Cannabidiol reverses myeloperoxidase hyperactivity in the prefrontal cortex and striatum, and reduces protein carbonyls in the hippocampus in a ketamine-induced schizophrenia rat model. Schizophrenia Research April 1, 2025
and 21 more in the library