Cannabinol shows neuroprotective potential: Insights from fruit fly study

Scientists also identified cannabinol analogs.

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Individuals above the age of 65 are most likely to develop an age-related neurological disorder, and the treatment options for them remain sparse.

Scientists are looking into the potential therapeutic benefits of cannabinoids, which are chemicals present in cannabis, such as THC and CBD. They have a particular interest in CBN, a lesser-known cannabinoid.

Scientists at the Salk Institute have discovered that CBN could protect the brain against neurodegeneration and aging. Additionally, they developed four brand-new CBN-based compounds that provided even more excellent brain protection. One of these novel chemicals helped treat fruit fly traumatic brain injury.

According to these results published in Redox Biology, CBN may be utilized to treat diseases like Parkinson’s and Alzheimer’s. Additional investigation on the effects of CBN may result in novel treatments for neurological conditions.

Research Professor Pamela Maher, the study’s senior author, said, “Not only does CBN have neuroprotective properties, but its derivatives have the potential to become novel therapeutics for various neurological disorders. We could pinpoint the active groups in CBN that are doing that neuroprotection, then improve them to create derivative compounds with greater neuroprotective ability and drug-like efficacy.”

Neurons in the brain can die due to various neurological illnesses; these deaths are frequently caused by dysfunction in the mitochondria, the brain cells’ powerhouses. CBN protects neurons by preventing mitochondrial malfunction. It wasn’t clear, though, how precisely CBN does this or whether its efficacy may be increased.

Scientists at the Salk Institute have found that CBN protects neurons against oxytocin/ferroptosis, a form of cell death, by controlling various aspects of mitochondrial function. They employed both academic and commercial techniques to increase CBN’s efficacy and gain a deeper understanding of its functioning.

To find the components of CBN that best protect neurons, scientists first divided them into smaller pieces. Then, tests were conducted on them to determine whether these four newly developed chemicals could protect neurons even more than CBN.

Zhibin Liang, first author and postdoctoral researcher in Maher’s lab, said“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. The four CBN analogs we landed on had improved medicinal chemical properties, which was exciting and important to our goal of using them as therapeutics.”

The researchers tested the four CBN analogs on human and mouse nerve cell cultures to assess how well they functioned. Three distinct methods were used to produce oxytocin and ferroptosis in these cells. They discovered that all four analogs 1) prevented the cells from dying and 2) possessed neuron-protecting properties comparable to those of ordinary CBN.

They then used Drosophila fruit flies to evaluate these effective analogs in a traumatic brain damage model. Among the analogs, CP1 was particularly successful in treating traumatic brain damage, as evidenced by the best rate of survival following the injury.

The results demonstrate CBN’s therapeutic potential and the scientific potential to reproduce and improve its drug-like qualities. Researchers are eager to find out if these substances can shield the brain from additional harm.

The scientists intend to investigate and improve the CBN analogs they have created in the future. To increase these chemicals’ capacity to shield brain cells, they will keep screening and analyzing them. They will pay particular attention to alterations in brain cells, particularly in mitochondria, and age-related neurodegeneration. Their objective is to create substances that resemble drugs, and that can support cellular health and guard against neural dysfunction as people age.

Journal Reference:

  1. Zhibin Liang, Alec Candib, David Soriano-Castell, Wolfgang Fischer, Kim Finley, Pamela Maher. Fragment-based drug discovery and biological evaluation of novel cannabinol-based inhibitors of oxytocin/ferroptosis for neurological disorders. Redox Biology. DOI: 10.1016/j.redox.2024.103138

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