Groundbreaking research has found that cannabinol (CBN), one of the less famous compounds of cannabis, may potentially aid in preventing and treating age-related neurodegenerative diseases, such as Alzheimer’s.
Scientists have a comprehensive understanding of the properties and effects of THC and CBD, two cannabis compounds that have become well known in recent years and analysed in research for decades. However, less is known about the therapeutic properties of cannabinol.
Now, a team of researchers from Salk have conducted a revolutionary study, discovering that CBN protects nerve cells from oxidative damage, a significant driver of cell death. The findings may help to devise novel strategies that employ cannabinol to mitigate a range of neurodegenerative diseases.
Pamela Maher, the senior author of the research and a research professor and head of Salk’s Cellular Neurobiology Laboratory, said: “We’ve found that cannabinol protects neurons from oxidative stress and cell death, two of the major contributors to Alzheimer’s. This discovery could one day lead to the development of new therapeutics for treating this disease and other neurodegenerative disorders, like Parkinson’s disease.”
The study was funded by the National Institutes of Health, the Paul F. Glenn Center for Biology of Aging Research at the Salk Institute, an Innovation Award from the Salk Institute, the Shiley Foundation, the Bundy Foundation, and the University of California San Diego.
What is cannabinol?
Cannabinol is derived from the cannabis plant, and although it is molecularly similar to THC, it does not share the same psychoactive properties and is subsequently less heavily regulated by the FDA. Previous research performed by Maher’s team identified that cannabinol has neuroprotective qualities, with this new research illuminating the mechanism in CBN that protects brain cells from damage and death.
Uncovering neuroprotective properties
The team investigated the process of oxytosis – otherwise known as ferroptosis – which is believed to occur in an ageing brain and may cause Alzheimer’s disease. Oxytosis can be triggered due to the gradual loss of the antioxidant glutathione, resulting in neural cell damage and death through lipid oxidation. The researchers administered cannabinol to nerve cells in their study and then introduced an agent to stimulate oxidative damage.
The results demonstrated that CBN works by protecting the mitochondria that power the cells within the neurons; oxidation causes mitochondria to curl up like doughnuts in damaged cells, a change displayed in the ageing cells of people with Alzheimer’s disease. The CBN treatment prevented this from happening to the mitochondria and enabled them to continue to function correctly. To reinforce their findings, the team replicated the experiment in nerve cells with no mitochondria; here, CBN no longer displayed its protective effect.
“We were able to directly show that maintenance of mitochondrial function was specifically required for the protective effects of the compound,” Maher said.
Additionally, the team identified that cannabinol did not activate cannabis receptors, which causes cannabinoids to produce a psychoactive response, meaning it could be administered without causing an individual to become “high”.
Zhibin Liang, the first author of the research and a postdoctoral fellow in the Maher lab, commented: “CBN is not a controlled substance like THC, the psychotropic compound in cannabis, and evidence has shown that CBN is safe in animals and humans. And because CBN works independently of cannabinoid receptors, CBN could also work in a wide variety of cells with ample therapeutic potential.”
“Mitochondrial dysfunction is implicated in changes in various tissues, not just in the brain and ageing, so the fact that this compound is able to maintain mitochondrial function suggests it could have more benefits beyond the context of Alzheimer’s disease,” Maher said.