Cannabinol (CBN) could help prevent neurodegenerative diseases such as Parkinson’s and Alzheimer’s according to new research by California’s Salk Institute.
Scientists have discovered how CBN protects nerve cells from oxidative damage, a major pathway to cell death, suggesting it has the potential to treat age-related conditions like Alzheimer’s.
Senior author, research professor and head of Salk’s cellular neurobiology laboratory Pamela Maher 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.”
Previous research by Professor Maher’s laboratory found CBN had neuroprotective properties, but it wasn’t clear how it worked. The new study explains the mechanism through which CBN protects brain cells from damage and death.
The team looked at the process of oxytosis, also called ferroptosis, which is thought to occur in the ageing brain and growing evidence suggests may be a cause of Alzheimer’s.
Oxytosis can be triggered by the gradual loss of an antioxidant called glutathione, causing neural cell damage and death via lipid oxidation. In the study, the scientists treated nerve cells with CBN, and then introduced an agent to stimulate oxidative damage.
They further found the CBN worked by protecting mitochondria, the cell’s powerhouses, within the neurons. In damaged cells, oxidation caused the mitochondria to curl up like doughnuts — a change that has also been seen in ageing cells taken from the brains of people with Alzheimer’s. Treating cells with CBN prevented the mitochondria from curling up and kept them functioning well.
To confirm the interaction between CBN and mitochondria, researchers then replicated the experiment in nerve cells that had the mitochondria removed. In these cells, CBN no longer demonstrated 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.
In another key finding, researchers showed CBN did not activate cannabinoid receptors, required to produce a psychoactive response, meaning it would work without causing the patient to get “high”.
First author Dr Zhibin Liang said: “Evidence has shown CBN is safe in animals and humans. And because [it] works independently of cannabinoid receptors, it could also work in a wide variety of cells with ample therapeutic potential.”
The study has implications for a range of neurodegenerative diseases such as Parkinson’s, which is also linked to glutathione loss.
Professor Maher added: “Mitochondrial dysfunction is implicated in changes in various tissues — not just in the brain and ageing.
“So the fact this compound is able to maintain mitochondrial function suggests it could have more benefits beyond the context of Alzheimer’s disease.”
She called for further research into CBN and other lesser-studied cannabinoids. The team are now working to see if they can reproduce the results in a pre-clinical mouse model.
