A recent study has found that cannabinol (CBN), a chemical compound found in the cannabis plant, can defend brain cells against cell death – common in people with neurodegenerative diseases like Parkinson’s disease, Alzheimer’s disease, and similar forms of dementia.
Cannabinol is molecularly similar to THC but is only mildly psychoactive. It is found in trace amounts in cannabis but can increase in content due to exposure to light, heat, oxygen, and time passing. For this reason, aged cannabis has higher amounts of CBN than fresh cannabis: THCA converts to CBNA over time, and CBNA converts to CBN via decarboxylation.
Cannabinol has been earmarked for its potential neuroprotective and anti-inflammatory qualities, positive influence on pain relief, and the immune system[i]. CBN appears to effectively keep ageing brain cells alive by regulating oxidative stress in cellular organelles. These subcellular structures perform specific jobs within the cell, such as storing genetic information or assembling proteins.
How Cannabinol Works in the Cells
Researchers at the Salk Institute for Biological Studies in San Diego, California, focused on how cannabinol can obstruct oxytosis – a form of programmed cell death strongly linked to age-related neurodegeneration. Also known as ferroptosis due to its link to iron, oxytosis results from the depletion of glutathione, an antioxidant, and leads to increased production of harmful reactive oxygen species and lethal calcium ions throughout the cell membrane. It is genetically and biochemically different from other forms of regulated cell death, such as apoptosis. The authors of the study artificially created this response by administering glutamate in high concentrations in the hippocampal cells, which resulted in neurons shrinking and changing shape – but they found that specific cells treated beforehand with CBN were undamaged after the administering of glutamate. This suggests that CBN may be effective in protecting the cells against oxytosis.
The study authors were then able to speculate over the potential of CBN to prevent premature cell death and protect against varying neurodegenerative diseases. With further experimentation, the team learned that without cannabinol, oxytosis/ferroptosis would lead to mitochondria curling up and ceasing to function – an effect observed in cells taken from the brains of people with Alzheimer’s disease – but the introduction of cannabinol would prevent these effects. In addition, CBN reduced the influx of calcium ions throughout the mitochondrial membranes and enabled these organelles to remain healthy and function normally.
The team then sought to confirm the interaction between CBN and mitochondria by repeating the experiment using cells engineered to be absent of mitochondria. They found that CBN was unable to prevent oxytosis in the neurons in these cells, suggesting that the compound’s ability to protect mitochondria from oxidative damage is the critical step for its potential as an effective treatment against certain types of programmed cell death[ii].
Study author and head of the Cellular Neurobiology Laboratory at Salk Institute, Pamela Maher, explained in a statement that “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.”[iii]
Healing without the High
Researchers were able to show that CBN did not activate cannabinoid receptors and, as such, would not produce a psychoactive response – in other words, CBN therapeutics would work without getting the patient stoned. First author Zhibin Liang commented that “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.”
Another positive is that CBN is not a controlled substance like THC in the US and is, therefore, less heavily regulated by the US Food and Drug Administration. This relaxed standard means CBN could potentially bypass red tape restrictions, which might otherwise delay its introduction for medical use. It is, however, controlled in the UK and some other jurisdictions.
The Salk Institute team now hopes to carry out further studies to see if they can reproduce the findings in a preclinical model involving mice.[i] https://pubchem.ncbi.nlm.nih.gov/compound/Cannabinol [ii]https://www.sciencedirect.com/science/article/abs/pii/S0891584922000016 [iii]https://www.salk.edu/news-release/active-ingredient-in-cannabis-protects-aging-brain-cells/