Study: CBD improves cognition in Alzheimer's disease

A two-week treatment with high doses of CBD helps restore the function of two proteins key to reducing the accumulation of beta-amyloid plaque, a hallmark of Alzheimer's disease, and improves cognition in an experimental model of early-onset familial Alzheimer's, reports a study recently.

TREM2 and IL-33 proteins are important for the ability of the brain's immune cells to literally consume dead cells and other debris such as the beta-amyloid plaque that accumulates in patients' brains, and levels of both are diminished in Alzheimer's disease.

Researchers report for the first time that cannabidiol normalizes the levels and function of these mechanisms, improving cognition as it also reduces levels of the immune protein IL-6, associated with the high levels of inflammation found in Alzheimer's disease, explains Dr Babak Baban, immunologist and author of the study.

«At present, we have two classes of drugs to treat Alzheimer's disease,» says Dr. John Morgan, neurologist and director of the Movement and Memory Disorders Programs in the Department of Neurology at the University of Toronto. Medical College of Georgia.

«One class increases levels of the neurotransmitter acetylcholine, which are also decreased in Alzheimer's disease, and another works through NMDA receptors involved in communication between neurons and important for memory. But we don't have anything that gets to the pathophysiology of the disease,» says study co-author Morgan.

CBD and Alzheimer's, effective on several levels

The researchers examined the CBD's ability to attack some of the brain's major systems affected by Alzheimer's disease.

They found that CBD appears to normalize levels of IL-33, a protein whose highest expression in humans is normally found in the brain, where it helps to sound the alarm in the presence of an «invader» such as beta-amyloid accumulation. There is also emerging evidence of its role as a regulatory protein, whose function of increasing or reducing the immune response depends on the environment. In Alzheimer's disease, this involves reducing inflammation and trying to restore balance to the immune system.

CBD also enhanced expression of the trigger receptor expressed on myeloid cells 2, or TREM2, which is found on the cell surface where it combines with another protein to transmit signals that activate cells, including immune cells. In the brain, its expression is on microglial cells, a special population of immune cells found only in the brain where they are essential for eliminating invaders such as a virus and irrevocably damaged neurons.

Low levels of TREM2 and rare variations in TREM2 are associated with Alzheimer's disease, and when tested on rodents, both TREM2 and IL-33 were low.

Both are essential to a natural and ongoing housekeeping process in the brain called phagocytosis, in which microglial cells regularly consume amyloid-beta, which is regularly produced in the brain as a result of the degradation of amyloid-beta precursor protein, which is important for the synapses, or connection points, between neurons, and which plaque interrupts.

They found that CBD treatment increased IL-33 and TREM2 levels seven- and tenfold, respectively.

Next steps include determining optimal doses and administering CBD earlier in the disease process. The compound was administered in the later stages of the published study, and now researchers are using it at the earliest signs of cognitive decline.

They also explore different ways to consume CBD, This included the use of an inhaler to help deliver CBD more directly to the brain. For the published studies, CBD was introduced into the bellies of mice every other day for two weeks.