Activating the body’s cannabinoid CB2 receptor, something done naturally by cannabis and certain cannabinoids, significantly reduced brain damage, inflammation and neurological impairment in mice following experimentally induced strokes, according to new research that also found the treatment helped preserve immune system function.
The study, published October 14 in the journal International Immunopharmacology, was conducted by researchers at Dalhousie University in Canada. It examined whether targeting CB2, a receptor involved in regulating inflammation and immune responses, could protect the brain from ischemic stroke while limiting the immune suppression that can follow severe brain injuries.
Researchers used male mice subjected to photothrombotic stroke, an experimental procedure that produces localized brain damage by interrupting blood flow. The animals received several cannabinoid receptor-targeting compounds before stroke induction, including HU-308, a synthetic compound that selectively activates CB2 without directly targeting the CB1 receptor primarily responsible for marijuana’s intoxicating effects.
Mice treated with HU-308 experienced smaller areas of damaged brain tissue, improved neurological outcomes and reduced expression of two major inflammatory markers, tumor necrosis factor (TNF) and interleukin-6 (IL-6), in the affected brain hemisphere. Researchers also found that activating both CB1 and CB2 receptors reduced stroke damage, but blocking CB2 eliminated those protective effects, indicating that CB2 played a central role.
The findings extended beyond brain protection. Strokes can trigger a condition known as central nervous system injury-induced immunodepression syndrome, which weakens the body’s ability to respond to infections. In untreated mice, strokes substantially reduced immune-cell responses to an inflammatory challenge, while HU-308 helped preserve the ability of white blood cells to adhere to blood vessel walls, an important part of the immune response.
Additional laboratory experiments involving microglia, the brain’s resident immune cells, showed that HU-308 reduced the release of TNF under inflammatory conditions. These findings provided further evidence that CB2 activation may help regulate damaging inflammation without broadly suppressing immune function.
The researchers concluded that selectively activating CB2 represents a promising approach to limiting acute stroke-related brain damage while helping maintain immune responsiveness.
The findings are preliminary and have not been tested in human stroke patients. Importantly, the experimental compounds were administered before strokes were induced, meaning the study does not establish whether CB2 activation would provide similar benefits when administered after a stroke has occurred.
