Cannabinoids Trigger Cellular Removal Of Alzheimer’s Disease-Associated Protein Plaques

Researchers at the Salk Institute in California have discovered that compounds found in cannabis – including tetrahydrocannabinol (THC) – may help neurons remove protein clumps of amyloid beta, which have been associated with Alzheimer’s disease. The experiments conducted on neurons in cell culture highlight the role of inflammation in the neurodegenerative disease, and could help drugmakers develop novel treatments.

“Although other studies have offered evidence that cannabinoids might be neuroprotective against the symptoms of Alzheimer’s, we believe our study is the first to demonstrate that cannabinoids affect both inflammation and amyloid beta accumulation in nerve cells,” said Dr. David Schubert, a professor at the Salk Institute and an author on the paper. The research was published in the journal, Aging and Mechanisms of Disease.

According to the National Institutes of Health (NIH), over five million Americans are affected by Alzheimer’s disease. The degenerative disease is the most common cause of dementia and is a leading cause of death in the US.

Amyloid beta protein begins to accumulate within the neurons of the brain even before any Alzheimer’s disease-associated symptoms begin to manifest. While amyloid beta plaques are associated with the disease, it’s unclear whether their formation is causative of Alzheimer’s.

In studying human nerve cells designed to overexpress amyloid beta protein, Schubert and his colleagues found that the high protein levels were associated with cellular inflammation and increased incidence of cell death. After exposing the cells to THC, the researchers found that the levels of amyloid beta protein were lowered, and the inflammatory response elicited by the protein plaques was eliminated.

“Inflammation within the brain is a major component of the damage associated with Alzheimer’s disease, but it has always been assumed that this response was coming from immune-like cells in the brain, not the nerve cells themselves,” said Antonio Currais, a postdoctoral researcher in Schubert’s laboratory and primary author on the paper. “When we were able to identify the molecular basis of the inflammatory response to amyloid beta, it became clear that THC-like compounds that the nerve cells make themselves, may be involved in protecting the cells from dying.”

Endocannabinoids – lipid molecules that are endogenously present in the brain – act as intercellular signals that bind to their receptors on adjacent neurons. As THC derived from cannabis is similar to the endocannabinoids found in the brain, it is also able to bind to those same receptors.

While the results point to THC and the endocannabinoid receptor as a potential target for future Alzheimer’s therapies, the researchers caution the studies so far have only been conducted in cell culture. In order to test the safety and efficacy of THC-like compounds on humans, the drug would need to be studied further in clinical trials.