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Introduction

Cannabidiol (CBD), one of the active components found in the marijuana plant promotes neurogenesis and can regulate inflammation in the brain. Neurogenesis is the growth of new neural pathways in the brain, which CBD has been shown to support, even in cells destroyed by trauma or old age. As more research has pointed to inflammationin the brain as one of the leading causes for neurodegenerative diseases, CBD has been getting more attention as a potential preventive treatment. This introductory article will try to summarize all the studies surrounding the use for CBD for Alzheimer’s disease (AD).

Background – What is Alzheimer’s Disease?

Alzheimer’s disease is a type of debilitating neurological condition characterized by the accumulation of amyloid-βand tau hyperphosphorylation,as well as oxidative stress and neuroinflammation. This illness, whose cause is yet to be known, is growing to epidemic proportions and most Americans over the age of fifty are afraid to be diagnosed with each passing day. A range of mutated genes as well as environmental toxins have been cited as some of the risk factors for neurodegenerative disorders.

Current AD Treatments

Proper diet, exercise, as well as social and educational engagement have been shown to help in maintaining a healthy brain. Nonetheless, there are no effective treatments that can successfully treat the symptoms associated by Alzheimer’s.

If nothing changes, researchers estimate that the number of people suffering from AD will triple in the next 50 years. So far, only five drugs exist for alleviating the cognitive symptoms caused by neurodegenerative conditions. As a result, there is dire need for more effective and safe treatment alternatives for not only the cognitive symptoms, but also the behavioral and psychological ones. Of the said drugs, two are derived from plants. This has stimulated a great deal of research in the recent years, with the hope of finding new therapeutic agents that can be relevant to the treatment of Alzheimer. Top on that list is cannabidiol (CBD).

Cannabidiol and its Effects on the Endocannabinoid System

CBD is among the main components of Cannabis sativa which lacks the psychoactive effects normally associated with the other main cannabinoid, Δ9-tetrahydrocannabinol (THC). CBD has been shown to have a wide range of therapeutic properties, including neuroprotective effectsin various pathological conditions.

CBD’s neuroprotection properties seem to be as a result of it’s antioxidant and anti-inflammatory activities, as well as its ability to modulate a wide range of neural targets (receptors and channels) that are implicated in the maintenance and development of neurodegenerative diseases. Besides Alzheimer’s, CBD is being investigated as a potential treatment for other pathological conditions such as: mood disorders, anxiety, depression, epilepsy and seizures, Parkinson’s disease, just to mention a few.

The Endocannabinoid System and the Treatment of Alzheimer’s Disease

In the past few years, targeting the endocannabinoid systemhas proven to be a promising therapeutic approach for treating Alzheimer’s and other types of dementia. The endocannabinoid system is comprised of cannabinoid receptors, including the well-researched CB1 and CB2 receptors, endogenous ligands as well as enzymes involved in the synthesis and degradation of these compounds.

Several findings indicatethat the activation of both CB1 and CB2 receptors whether by natural or synthetic agonists have beneficial effects towards AD, in experimental models, at non-psychotropic doses. Furthermore, endocannabinoid signaling has been shown to regulate numerous pathological processes. These include neuroinflammation, oxidative stress, excitotoxicity, and mitochondrial dysfunction.

What Does the Research on the use of CBD for Alzheimer’s Disease Say?

As mentioned above, the approved pharmacological treatments for AD seem to act only on symptoms without having any lasting effects on the disease itself. In the quest to find alternative strategies for stopping the progressive loss of neuronal cells, researchers have been focusedon investigating phytochemical compounds such as CBD, which show antioxidative, anti-inflammatory, anti-apoptotic and anti-amyloidogenic properties.

AD is many-sided in nature, and is associated with different mechanisms in the brain. This is a huge factor as to why there are no effective therapies that could slow down or deter the onset or development of this dreadful disease. It follows that the most suitable treatment for AD should be able to regulate the disease via multiple mechanisms, instead of targeting a single dysregulated pathway. To this end, cannabinoids such as CBD seem to be ahighly effective.

For starters, one study investigated whether pre-treatment with cannabidiol (CBD) moderated the transcriptional profile of mesenchymal stem cells (MSCs) derived from gingiva (GMSCs). this was done by performing a transcriptomic analysis. The authors hoped to improve the therapeutic potential of MSCs, which have emerged as a promising agent for the treatment of numerous neurodegenerative conditions, including Alzheimer’s disease.

The authors were able to prove that TRPV1 facilitates the regulatory effect of CBD on the PI3K/Akt/GSK3β axis. To put it briefly, the researchers concluded that pre-treatment with CBD prevented the expression of proteins potentially involved in the development of AD.

Other scientists have provided evidence suggesting that natural cannabinoids, including CBD, are effective in reducing memory impairment in AβPP/PS1 mice at advanced stages of Alzheimer’s disease. In this study, the authors noted that cannabinoids were not effective in altering the Aβ processing or in reducing the glial reactivity. This study also suggested that cannabinoids do not affect cognitive damage caused by healthy aging in wild-type mice. The experts recommended more studies to establish the full potential of CBD for Alzheimer’s disease.

In another study, mice were injected with human Abeta (1-42) peptide, and treated daily for seven days with 2.5 or 10 mg kg(-1), i.p. CBD. The mRNA for glial fibrillary acidic protein (GFAP) was analyzed using in situ hybridization. Also, protein expression of GFAP, IL-1beta and inducible nitric oxide synthase (iNOS) was established through immunofluorescence analysis. To conclude, ELISA assay of IL-1beta level and the measurement of NO were performed in dissected and homogenized ipsilateral hippocampi of the mice, in the absence or presence of CBD.

The results showed that CBD inhibited GFAP mRNA and protein expression in Abeta injected animals significantly, depending on the dose. Furthermore, under the same experimental conditions, CBD impaired iNOS and IL-1beta protein expression, and the related NO and IL-1beta release. The results of this study shed a light on the anti-inflammatory actions of CBD in vivo, proving that it is capable of reducing Abeta-induced neuroinflammatory responses.

A different study sought out to summarize the effects of CBD on Alzheimer’s using established pharmacological and transgenic animal models. In conclusion of the literature review, the researchers affirmed that CBD can promote neurogenesis, reduce reactive gliosis as well as neuroinflammation. Notably, CBD also reverses and prevents cognitive deficits in rodent models with Alzheimer’s. Interestingly, the authors noted that a combination therapy involving CBD and (THC), may mediate greater therapeutic benefits than using either phyto-cannabinoid unaccompanied. These studies stand as a “proof of principle” that CBD can be considered as a novel agent for the treatment of AD.

How CBD Works to Treat Alzheimer’s Disease – What scientists know so far

A few studies have focused on finding how CBD is able to manifest its various therapeutic properties with regards to Alzheimer’s disease. In one such study, scientists considered the impact of CB1 receptor deficiency on the development of AD by breeding amyloid precursor protein (APP) Swedish mutant mice (APP23) with CB1-deficient mice.

Even though most of the models died before attaining the proper age where AD starts to manifest, the surviving mice showed less APP levels. This suggested a modulatory influence of CB1 receptors on APP processing, that was further confirmed by modulating CB1 expression in vitro. Less APP levels were characterized by a reduction in plaque load and reduced inflammation in the CB1-deficient mice. However, in comparison to APP23 mice with healthy CB1 receptors, the CB1-deficient mice showed diminished learning and memory deficits. These data indicate that CB1 deficiency may worsen Alzheimer-related cognitive deficits and set CB1 as a potential target for treating AD.

A different study investigated the role of CBD in the regulation of APP processing in SHSY5Y(APP+) neurons. The same study also sought to establish the alleged involvement of peroxisome proliferator-activated receptor-γ (PPARγ) as a molecular site in control of CBD’s mechanisms. The outcome showed that CBD can induce the ubiquitination of APP protein, hence leading to a significant reduction in APP full length protein levels in SHSY5Y(APP+), as well as the consequent decrease in Aβ creation. Furthermore, CBD reduced the long-term apoptotic rate of SHSY5Y(APP+) neurons, hence promoting their chance of survival. More importantly, the results showed that CBD’s effects were dependent on the selective activation of PPARγ.

Conclusion

Clearly, pre-clinical evidence suggests that CBD has potential therapeutic effects in Alzheimer’s and other forms of dementia that are caused or worsened by inflammation. However, before we can employ CBD to treat AD, more concrete proof is needed from well-designed clinical studies. With the recent approval of Epidiolex, a new CBD-based drugs for treating rare forms of epilepsy, scientists and patients alike are hopeful that such a drug for Alzheimer’s may be developed and gain approval in the near future.

Below is a list of all the studies summarized in this article and more, concerning the use of CBD for Alzheimer’s disease. In case of any new developments with regards to CBD for AD, come back to this pageand we will be the first to let you know.

For more information on the use of CBD on treating other diseases, visit this page.

 

Research and Case Studies on the effects of Cannabis to treat Alzheimer’s: