# Exploring the neuroprotective effects of phytocannabinoids on oxygen-glucose deprived neurons in an in vitro model of stroke

## TL;DR

This study explores how certain plant-based cannabinoids may protect brain cells from stroke damage in a lab model.

## Contribution

The study identifies cannabigerorcinic acid (CBGOA) as a novel phytocannabinoid with potential neuroprotective effects in stroke.

## Key findings

- Cannabigerorcinic acid (CBGOA) significantly improved neuronal survival after oxygen-glucose deprivation.
- CBGOA did not affect caspase 3 activation, suggesting alternative neuroprotective pathways.
- The study used human iPSC-derived neurons, enhancing translational relevance for stroke research.

## Abstract

Stroke is a leading cause of death and disability worldwide, but therapeutic options to reduce or prevent neuronal damage are extremely limited. Cannabinoids exhibit antioxidant, anti-inflammatory, and receptor modulatory actions that may offer neuroprotection. While research on the potential of cannabinoids has expanded in epilepsy and neurodegeneration, the neuroprotective potential of this class of natural compounds in stroke remains underexplored. Here, we evaluated a panel of phytocannabinoids (PCs) for their ability to mitigate ischemia–reperfusion injury in an in vitro human model of stroke.

Human induced pluripotent stem cell (iPSC)-derived cortical neurons were subjected to 60 min of oxygen–glucose deprivation (OGD) followed by reperfusion. Neuronal survival was quantified over seven days using longitudinal live-cell imaging. Twenty-eight PCs were screened for their effect on reducing neuronal death.

Among 28 PCs screened, seven demonstrated modest effects, with cannabigerorcinic acid (CBGOA) significantly improving post-OGD neuronal survival. While OGD exposure led to increased cell death via activation of caspase 3, CBGOA treatment did not impact that pathway, suggesting that other caspase-independent pathways may be implicated.

This pilot study identifies CBGOA as a candidate cannabinoid with neuroprotective potential in an in vitro model of ischemic stroke. The use of iPSC-derived human cortical neurons strengthens translational relevance, but the modest effects observed, and the limitations of in vitro systems, underscore the need for in vivo validation and further mechanistic studies. Collectively, these results provide a foundation for exploring CBGOA and related cannabinoids as potential neuroprotective agents in stroke.

The online version contains supplementary material available at 10.1186/s42238-026-00393-0.