Unraveling Cannabidiol's Dual Modulatory Role in Schizophrenia: Network Pharmacology and In Vivo Validation of Neuroinflammatory and Behavioral Modulation
Ying Wei, Xiang Liu, Shijun Lin, Zhiwei Jia, Lin Liu, Baiqiang Wang, Lin-Chuan Liao, Xue Mei
Molecular Neurobiology December 10, 2025 DOI: 10.1007/s12035-025-05608-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study combining network pharmacology, in vitro cell experiments, and in vivo animal experiments Peer reviewed |
|---|---|
| Population | BV2 microglial cells in vitro and a ketamine-induced animal model of schizophrenia-like symptoms in vivo |
| Intervention | Cannabidiol (CBD) |
| Dose | 10 mg/kg, i.p. |
| Duration | 5 consecutive days of treatment |
| Topics | CBD |
| Key findings | CBD reduced pro-inflammatory cytokines in BV2 microglial cells and in the plasma and brain tissue of ketamine-treated animals, modulated the 5HT1AR-MAPK pathway, and alleviated schizophrenia-like behaviors including anxiety, spatial memory, and social behavior. The authors argue these findings suggest CBD has potential therapeutic benefits for schizophrenia, though clinical trials are needed. |
Abstract
Schizophrenia (SCZ), a chronic psychiatric disorder, is characterized by cognitive impairment, hallucinations, and delusions, with current antipsychotic treatments offering limited efficacy and considerable side effects. Cannabidiol (CBD), a non-psychoactive compound from Cannabis sativa, has shown promise in treating neurological and psychiatric conditions, though its precise mechanisms in schizophrenia remain unclear. Using network pharmacology, this study predicts CBD’s targets and pathways in schizophrenia, highlighting LPS-induced neuroinflammation and implicating 5-HT1AR-MAPK signaling as one potential contributor. In vitro, CBD (10 mg/kg, i.p.) treatment significantly reduced pro-inflammatory cytokines (e.g., NO, IL-1β, IL-6, TNF-α) and modulated the 5HT1AR-MAPK pathway, including increased 5HT1AR expression and decreased MAPK/ERK1/2 phosphorylation (p < 0.05). In vivo, CBD alleviated SCZ-like symptoms in a ketamine-induced animal model, reducing anxiety in the open field (p < 0.01) and elevated plus maze tests (p < 0.01), improving spatial memory in the Y-maze (p < 0.01) and social behavior (p < 0.0001) after 5 consecutive days of treatment. Critically, we validated CBD’s central anti-inflammatory effects by demonstrating reduced pro-inflammatory cytokine levels in both plasma and brain tissues (p < 0.05). Further correlation analysis established a direct link between brain cytokine suppression and behavioral improvements, integrating in vitro findings from BV2 microglial cells with in vivo neuroinflammatory and behavioral outcomes.These findings suggest the potential therapeutic benefits of CBD for SCZ, though further research, particularly clinical trials, is required to validate its efficacy and establish it as a novel therapeutic strategy.
Comparable studies
Other preclinical and animal studies on CBD, most cited first.
Citations in the library
Cites 10
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- Schizophrenia-like endurable behavioral and neuroadaptive changes induced by ketamine administration involve Angiotensin II AT1receptor. Behavioural Brain Research February 23, 2022
- Phytocannabinoids and schizophrenia: Focus on adolescence as a critical window of enhanced vulnerability and opportunity for treatment. Pharmacological Research December 1, 2021
- CBD Effects on Motor Profile and Neurobiological Indices Related to Glutamatergic Function Induced by Repeated Ketamine Pre-Administration Frontiers in Pharmacology October 27, 2021
and 5 more in the library