Alzheimer’s disease is an progressive brain disorder that slowly destroys memory and thinking skills, and eventually the ability to carry out the simplest tasks. In most people (~95%), symptoms first appear in their mid-60s, however, there is autosomal dominant genetic form of the disease in which the symptoms onset earlier in life. Regardless of the cause, two unique findings in the brain are associated with the disease: 1) amyloid plaques deposition between the brain cells and 2) the deposition of protein fibers within the brain cells called neurofibrillary tangles, both of which lead to a loss of connections between brain cells. Amyloid plaques consist of normal protein fragments that are normally eliminated from the brain but in AD, these proteins accumulate and form hard, insoluble plaques. Neurofibrillary tangles are made up of microtubules that are normally found in the brain and function to transport materials within the nerve cells so they can function normally. However, in AD, the protein that makes up these fibers (tau) is abnormal and causes the tubules to collapse, resulting in abnormal nerve cell function. These pathologically findings cause inflammation and oxidative stress in the brain all of which causes and promotes neurodegeneration. In general, as the symptoms of AD deteriorate, the plaques and tangles become more pronounced and the neuroinflammation and oxidative stress increase. Alzheimer’s has been thought to be continually progressive and irreversible, however, recent studies suggest that this may not be completely true.
In the laboratory CBD protects brain cells, prevents nerve degeneration, decreases plaques, is anti-inflammatory, decreases oxidative stress, and improves cell life. Each of these effects would be beneficial in AD. In addition, CBD decreases the production of amyloid plaques. In animal models of AD, CBD has the same effects and, as it has these effects, the memories and thinking process of the animals improve. CBD even improves the memories and thinking processes of animals with advanced AD. Very little human research using CBD to treat AD has been done. However, in a small 4-week study of 10 human patients with advanced AD, CBD improved their symptoms.
CBD has been found in-vitro: to be neuroprotective, to prevent hippocampal and cortical neurodegeneration, to reduce tau hyperphosphorylation, to lower amyloid b levels, to be anti-inflammatory, and to act as an antioxidant. 1-5 In addition, CBD protects against Ab mediated neurotoxicity and microglial- activated neurotoxicity and improves cell viability.6-8 CBD decreases the oxidative stress in neuroinflammation.9 GPR3 is a modulator of beta-arrestin 2 (BA2) and its stimulation by agonists results in over production of BA2 while its stimulation by inverse agonists results in lowering of BA2.10 Beta-arrestin 2 (BA2) is produced by stimulation of GPR3 receptors and results in the production of amyloid in human brain cultures.10
Live Animal Studies
CBD reduces inflammation by reducing NO and interleukin-1b (IL-1b) release.11 IL-1b is involved in neurodegeneration and the over-production of NO, which causes tau hyperphosphorylation. In addition, CBD is an inverse agonist for GPR3 which when stimulated inversely should result in decreased production of amyloid in brain tissue and subsequently a decrease in the number of plaques.12 Eradiation of GPR3 results in the loss of plaques and the restoration of memory in a mice model of AD.13 In both mice and rat models of AD, CBD was able to reverse the pathological changes found in AD. 4,7,12-20 CBD has been found restore memory and other cognitive defects in animals that have the disease—even in animals with advanced disease.4,7,13,14,17,19,20 Finally, CBD has been shown to prevent the development of AD.21
GPR3 expression is elevated in the sporadic Alzheimer’s disease brain, is highly expressed in areas of the normal human brain implicated in Alzheimer’s disease and this upregulation correlates with the progression of the disease 13,22. Over a 4-week period involving 10 patients, CBD decreased the amount and severity of delusions, agitation/aggression, irritability, and apathy of patients with AD and improved the amount of sleep in these patients. In addition, it decreased the amount and severity of caregiver distress. No adverse reactions were noted during the treatment time.23
CBD significantly reverses the neural pathology in animal models of Alzheimer’s Disease and improves the memory and thinking of the animals. Whether this will translate to humans is not yet scientifically proven. However, a small, non-controlled study indicates promise. At this time, the FDA does not recommend CBD for the treatment of Alzheimer’s Disease
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