CBD: Improvements Against Familial Alzheimer’s Disease

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  • Intense CBD treatments have shown improvements in hereditary Alzheimer’s disease. Very preliminary research, but showing that CBD opens up a lot of therapeutic avenues.

    Intense CBD treatments have shown improvements in hereditary Alzheimer's disease. Very preliminary research, but showing that CBD opens up a lot of therapeutic avenues.

    Treatment of high doses of CBD for two weeks helps restore function of two key proteins to reduce the build-up of beta-amyloid plaque, a hallmark of Alzheimer’s disease, and improves cognition in an experimental familial Alzheimer’s model early, the researchers report.

    CBD improves cognition

    TREM2 and IL-33 proteins are important for the ability of immune cells in the brain to literally consume dead cells and other debris like beta-amyloid plaque that builds up in patients’ brains and levels of both are lowered in Alzheimer’s disease.

    Researchers report for the first time that CBD normalizes levels and function, improving cognition as it also lowers levels of the immune protein IL-6, which is associated with the high levels of inflammation found in Alzheimer’s disease, says Dr. Babak Baban, immunologist and associate dean of research at Georgia Dental College and corresponding author of the study.

    There is an urgent need for new therapies to improve outcomes for patients with this disease, which is considered one of the fastest growing health threats in the United States according to analysts at DCG and the Medical College of Georgia write in the Journal of Alzheimer’s Disease.

    CBD works on several levels against Alzheimer’s

    “Right now we have two classes of drugs to treat Alzheimer’s disease,” says Dr. John Morgan, neurologist and director of movement and memory disorders programs in the Department of Neurology at MCG. One treatment increases the levels of the neurotransmitter acetylcholine, which is also lowered 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 addresses the pathophysiology of the disease,” says Morgan, co-author of the study.

    Analysts at DCG and MCG have decided to examine the ability of CBD to attack some of the major brain systems that go wrong in 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 sound the alarm that there is a invader such as the build-up of beta-amyloid.

    There is also emerging evidence for its role as a regulatory protein, the function of which to increase or decrease the immune response depends on the environment, Baban says. In Alzheimer’s disease, that involves reducing inflammation and trying to restore balance to the immune system, he says.

    An improvement in phagocytosis

    CBD also enhanced the 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 cells. immune.

    In the brain, it is expressed on microglial cells, a special population of immune cells found only in the brain where they are essential for clearing invaders like viruses and irrevocably damaged neurons.

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

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

    Visible improvements in mice

    They found that the CBD treatment increased IL-33 and TREM2 levels seven-fold and ten-fold, respectively. The impact of CBD on brain function in the mouse model of early Alzheimer’s disease has been assessed by methods such as the ability to differentiate a familiar from a new one, as well as by observing rodent movement.

    People with Alzheimer’s disease may experience movement problems like stiffness and impaired gait, says Dr. Hesam Khodadadi, a graduate student working in Baban’s lab. Mice with the disease move in an endless inner circle, a behavior that stopped with the CBD treatment, says Khodadadi, the study’s first author.

    The 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 analysts are using it at the first signs of cognitive decline, Khodadadi says.

    Inhaling CBD as a mode of absorption

    They are also exploring delivery systems, including the use of an inhaler that should help deliver CBD more directly to the brain. For published studies, CBD was introduced into the stomachs of mice every other day for two weeks.

    One company developed animal and human inhalers for researchers who also explored the effect of CBD on adult respiratory distress syndrome, or ARDS, a buildup of fluid in the lungs that is a major and fatal complication of COVID-19 as well as other serious illnesses like sepsis and major trauma.

    The doses of CBD used for the Alzheimer’s disease study were the same as those used successfully by researchers to reduce the “cytokine storm” of ARDS, which can irrevocably damage the lungs. Familial disease is a hereditary version of Alzheimer’s disease in which symptoms usually surface at ages 30 and 40 and occur in about 10 to 15% of patients.

    Effective against both standard and hereditary Alzheimer’s

    CBD is expected to be at least as effective in the more common non-familial Alzheimer’s disease, which likely has more targets for CBD, Baban notes. They are already looking at its potential in a more common model of this type and are moving forward to establish a clinical trial.

    Plaques along with neurofibrillary tangles, a collection of the tau protein inside neurons, are the main building blocks of Alzheimer’s disease, Morgan says. Beta-amyloid usually appears in the brain 15 to 20 years or more before dementia, he says, and the appearance of tau tangles, which can occur up to 10 years after, correlates with the onset of dementia. dementia.

    There is some interaction between beta-amyloid and tau that decreases the dysfunction of each, Morgan notes. The Food and Drug Administration is expected to make a decision in early June 2021 on a new drug aducanumab, which would be the first to attack and help eliminate beta-amyloid, Morgan says.

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