The Effects of Cannabinoids on Ischemic Stroke-Associated Neuroinflammation: A Systematic Review

Stroke represents a significant burden on global health and the economy, with high mortality rates, disability, and recurrence. Ischemic stroke is a serious condition that occurs when a blood vessel in the brain is interrupted, reducing the blood supply to the affected area. Inflammation is a significant component in stroke pathophysiology. Neuroinflammation is triggered following the acute ischemic ictus, where the blood-brain barrier (BBB) breaks down, causing damage to the endothelial cells. The damage will eventually generate oxidative stress, activate the pathological phenotypes of astrocytes and microglia, and lead to neuronal death in the neurovascular unit. As a result, the brain unleashes a robust neuroinflammatory response, which can further worsen the neurological outcomes. Neuroinflammation is a complex pathological process involved in ischemic damage and repair. Finding new neuroinflammation molecular targets is essential to develop effective and safe novel treatment approaches against ischemic stroke. Accumulating studies have investigated the pharmacological properties of cannabinoids (CBs) for many years, and recent research has shown their potential therapeutic use in treating ischemic stroke in rodent models. These findings revealed promising impacts of CBs in reducing neuroinflammation and cellular death and ameliorating neurological deficits. In this review, we explore the possibility of the therapeutic administration of CBs in mitigating neuroinflammation caused by a stroke. We summarize the results from several preclinical studies evaluating the efficacy of CBs anti-inflammatory interventions in ischemic stroke. Although convincing preclinical evidence implies that CBs targeting neuroinflammation are promising for ischemic stroke, translating these findings into the clinical setting has proven to be challenging. The translation hurdle is due to the essence of the CBs ability to cause anxiety, cognitive deficit, and psychosis. Future studies are warranted to address the dose-beneficial effect of CBs in clinical trials of ischemic stroke-related neuroinflammation treatment.