Researchers at the Salk Institute, a non-profit research organisation, have found that the cannabinoid CBN (cannabinol) may be able to treat neurological disorders such as Alzheimer’s and Parkinson’s disease.
In the study, published in the journal Redox Biology, researchers first used existing data from previous studies to understand how naturally occurring CBN has helped to preserve brain cells in previous tests. CBN is believed to support mitochondrial activity, which is an important part of brain cell survival and energy production. Mitochondrial dysfunction is a common feature in several neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease.
After analysing data, the researchers studied CBN, breaking the compound down into smaller chemical fragments to understand which parts of the molecule were most effective at protecting neurons in the brain, enabling them to identify the most effective components. From this, the researchers then created four CBD analogues, chemically similar compounds, which they believed would go on to be the most effective.
“We were looking for CBN analogs that could get into the brain more efficiently, act more quickly, and produce a stronger neuroprotective effect than CBN itself,” said Zhibin Liang, one of the study authors. “The four CBN analogs we landed on had improved medicinal chemical properties, which was exciting and really important to our goal of using them as therapeutics.”
The CBD analogues were then tested in the lab, or in vitro, using cultured nerve cells from mice and humans. The researchers induced three types of cell death processes that mimic those occurring in the brains of people who have neurodegenerative diseases. By applying the newly created CBN analogues to these cultured nerve cells, they were able to assess the protective capabilities of the analogues compared to standard CBN.
After the successful in vitro tests, the analogues were then tested in live subjects of Drosophila fruit flies. The fruit flies were subjected to conditions that simulated traumatic brain injury, and the researchers measured the survival rates to gauge the effectiveness of the CBN analogues, with one analogue, CP1, showing excellent results in enhancing survival post-injury.
“Our findings help demonstrate the therapeutic potential of CBN, as well as the scientific opportunity we have to replicate and refine its drug-like properties,” Maher said. “Could we one day give this CBN analog to football players the day before a big game, or to car accident survivors as they arrive in the hospital? We’re excited to see how effective these compounds might be in protecting the brain from further damage.”
While testing on fruit flies allows for rapid results when learning about a compound in a live model, it has limitations. Fruit flies differ physiologically from humans, meaning the results of these early tests might not yet be replicable in human testing, however, the researchers remain cautiously optimistic. “Not only does CBN have neuroprotective properties, but its derivatives have the potential to become novel therapeutics for various neurological disorders,” said senior author Professor Pamela Maher. “We were able to pinpoint the active groups in CBN that are doing that neuroprotection, then improve them to create derivative compounds that have greater neuroprotective ability and drug-like efficacy.
“Our findings help demonstrate the therapeutic potential of CBN, as well as the scientific opportunity we have to replicate and refine its drug-like properties,” Maher said. “Could we one day give this CBN analog to football players the day before a big game, or to car accident survivors as they arrive in the hospital? We’re excited to see how effective these compounds might be in protecting the brain from further damage.”
