Study: Cannabinerol (CBNR) May Counteract Alzheimer’s-Related RNA Splicing Defects

The study focused on how CBNR affects RNA splicing in an in vitro model using SH-SY5Y cells exposed to beta-amyloid (Aβ), a protein commonly associated with AD. The researchers had previously shown that CBNR helps protect against Aβ-induced cell death. In this new study, they examined whether CBNR could correct disruptions in alternative mRNA splicing—a mechanism increasingly recognized as a contributor to AD progression.

Using a computational tool known as rMATS, the researchers identified 96 differential alternative splicing events (DASEs) altered by Aβ. Remarkably, all of these were restored to normal by CBNR pre-treatment. Many of the changes involved retained introns (RIs) containing premature stop codons, which can disrupt protein formation. CBNR appeared to reduce the frequency of these RIs back to typical levels. The study also uncovered 33 possible interactions between DASE regions and miRNAs linked to AD, pointing to broader genetic regulatory effects. Pathway analysis highlighted that many of the restored genes were part of the “Alzheimer’s disease-amyloid secretase pathway,” a key biological process implicated in the development of AD.

According to the authors, this is the first evidence showing a cannabinoid can modulate mRNA splicing in an Alzheimer’s disease model, suggesting a new potential mechanism for cannabinoid-based neuroprotection.