Study: CBD improves function in early-onset Alzheimer’s patients

Researchers have found that high doses of CBD could help restore function in early-onset Alzheimer’s.

A two-week course of high doses of CBD helps reduce the accumulation of beta-amyloid plaque – a hallmark of Alzheimer’s disease –  and improves cognition, investigators report.

Proteins TREM2 and IL-33 are important to the ability of the brain to consume dead cells and other debris like the beta-amyloid plaque that piles up in patients’ brains – both of which are reduced in Alzheimer’s patients.

Researchers have reported for the first time that CBD normalises levels and function, improving cognition in an experimental model of early onset familial Alzheimer’s.

CBD also reduces levels of the immune protein IL-6, which is associated with the high inflammation levels found in Alzheimer’s, says Dr Babak Baban, immunologist and associate dean for research in the Dental College of Georgia and the study’s corresponding author.

There is a dire need for novel therapies to improve outcomes for patients with this condition, which is considered one of the fastest-growing health threats in the United States, DCG and Medical College of Georgia investigators write in the Journal of Alzheimer’s Disease.

“Right now we have two classes of drugs to treat Alzheimer’s,” says co-author, Dr John Morgan, neurologist and director of the Movement and Memory Disorder Programs in the MCG Department of Neurology. 

“One class increases levels of the neurotransmitter acetylcholine, which also are decreased in Alzheimer’s, and the other works through the NMDA receptors involved in communication between neurons and important to memory. 

“But we have nothing that gets to the pathophysiology of the disease.”

The DCG and MCG investigators explored CBD’s ability to address some of the key brain systems that go awry in Alzheimer’s.

It appears to normalise levels of IL-33, a protein found in the brain, which helps sound the alarm that there is an invader like the beta-amyloid accumulation. 

There is also emerging evidence of its role as a regulatory protein, reducing inflammation and restoring balance in the immune system, Baban says.

CBD also improved expression of triggering receptors of TREM2, which is found on the cell surface where it combines with another protein to transmit signals that activate immune cells.

Low levels of TREM2 and rare variations in TREM2 are associated with Alzheimer’s, and in their mouse model TREM2 and IL-33 were both low.

They found CBD treatment increased levels of IL-33 and TREM2 — sevenfold and tenfold, respectively.

CBD’s impact on brain function in the mouse model of early onset Alzheimer’s was assessed by methods like the ability to differentiate between a familiar item and a new one, as well as observing the rodents’ movement.

People with Alzheimer’s may experience movement problems like stiffness and an impaired gait, says Dr Hesam Khodadadi, a graduate student working in Baban’s lab. 

Mice with the disease run in an endless tight circle, behavior which stopped with CBD treatment, says Khodadadi, the study’s first author.

Next steps include determining optimal doses and giving CBD earlier in the disease process. The compound was given in the late stages for the published study, and now the investigators are using it at the first signs of cognitive decline, Khodadadi says.

They also are exploring delivery systems including the use of an inhaler that should help deliver the CBD more directly to the brain. 

Familial disease is an inherited version of Alzheimer’s in which symptoms typically surface in the 30s and 40s and occurs in about 10-15 percent of patients.

CBD should be at least equally effective in the more common, nonfamilial type Alzheimer’s, which likely have more targets for CBD, Baban notes. Researchers are already looking at its potential in a model of this more common type and moving forward to establish a clinical trial.

The Food and Drug Administration is scheduled to make a ruling by early June on a new drug aducanumab, which would be the first to attack and help clear beta amyloid.

Read the full study.